diff --git a/.github/workflows/emscripten.yml b/.github/workflows/emscripten.yml
index d6f512925..1f8648015 100644
--- a/.github/workflows/emscripten.yml
+++ b/.github/workflows/emscripten.yml
@@ -77,6 +77,34 @@ jobs:
             llvm_enable_projects: "clang;lld"
             llvm_targets_to_build: "WebAssembly"
             emsdk_ver: "3.1.73"
+          - name: ubu24-arm-clang-repl-21-emscripten
+            os: ubuntu-24.04-arm
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang;lld"
+            llvm_targets_to_build: "WebAssembly"
+            emsdk_ver: "3.1.73"
+          - name: osx15-arm-clang-repl-21-emscripten
+            os: macos-15
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang;lld"
+            llvm_targets_to_build: "WebAssembly"
+            emsdk_ver: "3.1.73"
+          - name: ubu24-x86-clang-repl-21-emscripten
+            os: ubuntu-24.04
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang;lld"
+            llvm_targets_to_build: "WebAssembly"
+            emsdk_ver: "3.1.73"
+          - name: win2025-x86-clang-repl-21-emscripten
+            os: windows-2025
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang;lld"
+            llvm_targets_to_build: "WebAssembly"
+            emsdk_ver: "3.1.73"
 
     steps:
     - uses: actions/checkout@v5
@@ -199,7 +227,7 @@ jobs:
         else
           # Apply patches
           llvm_vers=$(echo "${{ matrix.clang-runtime }}" | tr '[:lower:]' '[:upper:]')
-          if [[ "${llvm_vers}" == "19" || "${llvm_vers}" == "20" ]]; then
+          if [[ "${llvm_vers}" == "19" || "${llvm_vers}" == "20" || "${llvm_vers}" == "21"  ]]; then
             git apply -v ../patches/llvm/emscripten-clang${{ matrix.clang-runtime }}-*.patch
             echo "Apply emscripten-clang${{ matrix.clang-runtime }}-*.patch patches:"
           fi
@@ -325,6 +353,11 @@ jobs:
             git apply -v emscripten-clang20-2-shift-temporary-files-to-tmp-dir.patch
             git apply -v emscripten-clang20-3-enable_exception_handling.patch
           }
+          elseif ( "${{ matrix.clang-runtime }}" -imatch "21" )
+          {
+            git apply -v emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch
+            git apply -v emscripten-clang21-2-enable_exception_handling.patch
+          }
           cd build
           echo "Apply clang${{ matrix.clang-runtime }}-*.patch patches:"
           emcmake cmake -DCMAKE_BUILD_TYPE=Release `
@@ -437,6 +470,30 @@ jobs:
             cling: Off
             micromamba_shell_init: powershell
             emsdk_ver: "3.1.73"
+          - name: ubu24-x86-clang-repl-21-emscripten_wasm
+            os: ubuntu-24.04
+            clang-runtime: '21'
+            cling: Off
+            micromamba_shell_init: bash
+            emsdk_ver: "3.1.73"
+          - name: osx15-arm-clang-repl-21-emscripten_wasm
+            os: macos-15
+            clang-runtime: '21'
+            cling: Off
+            micromamba_shell_init: bash
+            emsdk_ver: "3.1.73"
+          - name: ubu24-arm-clang-repl-21-emscripten_wasm
+            os: ubuntu-24.04-arm
+            clang-runtime: '21'
+            cling: Off
+            micromamba_shell_init: bash
+            emsdk_ver: "3.1.73"
+          - name: win2025-x86-clang-repl-21-emscripten
+            os: windows-2025
+            clang-runtime: '21'
+            cling: Off
+            micromamba_shell_init: powershell
+            emsdk_ver: "3.1.73"
 
     steps:
     - uses: actions/checkout@v5
diff --git a/.github/workflows/main.yml b/.github/workflows/main.yml
index ac9450d0b..c72184eaf 100644
--- a/.github/workflows/main.yml
+++ b/.github/workflows/main.yml
@@ -23,6 +23,14 @@ jobs:
       matrix:
         include:
           # Ubuntu Arm Jobs
+          - name: ubu24-arm-gcc12-clang-repl-21
+            os: ubuntu-24.04-arm
+            compiler: gcc-12
+            clang-runtime: '21'
+            cling: Off
+            cppyy: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host;NVPTX"
           - name: ubu22-arm-gcc12-clang-repl-20-coverage
             os: ubuntu-22.04-arm
             compiler: gcc-12
@@ -66,6 +74,14 @@ jobs:
             llvm_enable_projects: "clang"
             llvm_targets_to_build: "host;NVPTX"
           # Ubuntu X86 Jobs
+          - name: ubu24-x86-gcc12-clang-repl-21
+            os: ubuntu-24.04
+            compiler: gcc-12
+            clang-runtime: '21'
+            cling: Off
+            cppyy: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host;NVPTX"
           - name: ubu24-x86-gcc12-clang-repl-20
             os: ubuntu-24.04
             compiler: gcc-12
@@ -100,6 +116,14 @@ jobs:
             llvm_enable_projects: "clang"
             llvm_targets_to_build: "host;NVPTX"
           # MacOS Arm Jobs
+          - name: osx15-arm-clang-clang-repl-21
+            os: macos-15
+            compiler: clang
+            clang-runtime: '21'
+            cling: Off
+            cppyy: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host"
           - name: osx15-arm-clang-clang-repl-20
             os: macos-15
             compiler: clang
@@ -134,6 +158,14 @@ jobs:
             llvm_enable_projects: "clang"
             llvm_targets_to_build: "host;NVPTX"
           # MacOS X86 Jobs
+          - name: osx15-x86-clang-clang-repl-21
+            os: macos-15-intel
+            compiler: clang
+            clang-runtime: '21'
+            cling: Off
+            cppyy: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host"
           - name: osx15-x86-clang-clang-repl-20
             os: macos-15-intel
             compiler: clang
@@ -168,6 +200,13 @@ jobs:
             llvm_enable_projects: "clang"
             llvm_targets_to_build: "host;NVPTX"
           # Windows Arm Jobs
+          - name: win11-msvc-clang-repl-21
+            os: windows-11-arm
+            compiler: msvc
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host;NVPTX"
           - name: win11-msvc-clang-repl-20
             os: windows-11-arm
             compiler: msvc
@@ -184,6 +223,13 @@ jobs:
             llvm_enable_projects: "clang"
             llvm_targets_to_build: "host;NVPTX"
           # Windows X86 Jobs
+          - name: win2025-msvc-clang-repl-21
+            os: windows-2025
+            compiler: msvc
+            clang-runtime: '21'
+            cling: Off
+            llvm_enable_projects: "clang"
+            llvm_targets_to_build: "host;NVPTX"
           - name: win2025-msvc-clang-repl-20
             os: windows-2025
             compiler: msvc
diff --git a/CMakeLists.txt b/CMakeLists.txt
index 5d1aa034d..1850ddcc4 100644
--- a/CMakeLists.txt
+++ b/CMakeLists.txt
@@ -68,14 +68,14 @@ include(GNUInstallDirs)
   ## Define supported version of clang and llvm
 
   set(CLANG_MIN_SUPPORTED 18.0)
-  set(CLANG_MAX_SUPPORTED "20.1.x")
-  set(CLANG_VERSION_UPPER_BOUND 21.0.0)
+  set(CLANG_MAX_SUPPORTED "21.1.x")
+  set(CLANG_VERSION_UPPER_BOUND 22.0.0)
   set(LLD_MIN_SUPPORTED 18.0)
-  set(LLD_MAX_SUPPORTED "20.1.x")
-  set(LLD_VERSION_UPPER_BOUND 21.0.0)
+  set(LLD_MAX_SUPPORTED "21.1.x")
+  set(LLD_VERSION_UPPER_BOUND 22.0.0)
   set(LLVM_MIN_SUPPORTED 18.0)
-  set(LLVM_MAX_SUPPORTED "20.1.x")
-  set(LLVM_VERSION_UPPER_BOUND 21.0.0)
+  set(LLVM_MAX_SUPPORTED "21.1.x")
+  set(LLVM_VERSION_UPPER_BOUND 22.0.0)
 
   ## Set Cmake packages search order
 
diff --git a/Emscripten-build-instructions.md b/Emscripten-build-instructions.md
index 0854fed2d..f7c40673b 100644
--- a/Emscripten-build-instructions.md
+++ b/Emscripten-build-instructions.md
@@ -42,11 +42,11 @@ $env:PWD_DIR= $PWD.Path
 $env:SYSROOT_PATH="$env:EMSDK/upstream/emscripten/cache/sysroot"
 ```
 
-Now clone the 20.x release of the LLVM project repository and CppInterOp (the building of the emscripten version of llvm can be
+Now clone the 21.x release of the LLVM project repository and CppInterOp (the building of the emscripten version of llvm can be
 avoided by executing micromamba install llvm -c <https://repo.mamba.pm/emscripten-forge> and setting the LLVM_BUILD_DIR/$env:LLVM_BUILD_DIR appropriately)
 
 ```bash
-git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
 git clone --depth=1 https://github.com/compiler-research/CppInterOp.git
 ```
 
@@ -55,16 +55,16 @@ executing
 
 ```bash
 cd ./llvm-project/
-git apply -v ../CppInterOp/patches/llvm/emscripten-clang20-*.patch
+git apply -v ../CppInterOp/patches/llvm/emscripten-clang21-*.patch
 ```
 
 On Windows execute the following
 
 ```powershell
 cd .\llvm-project\
-cp -r ..\patches\llvm\emscripten-clang20*
-git apply -v emscripten-clang20-2-shift-temporary-files-to-tmp-dir.patch
-git apply -v emscripten-clang20-3-enable_exception_handling.patch
+cp -r ..\patches\llvm\emscripten-clang21*
+git apply -v emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch
+git apply -v emscripten-clang21-2-enable_exception_handling.patch
 ```
 
 We are now in a position to build an emscripten build of llvm by executing the following on Linux
@@ -343,7 +343,7 @@ of llvm you are building against)
 ```bash
 cd ../..
 git clone --depth=1 https://github.com/compiler-research/xeus-cpp.git
-export LLVM_VERSION=20
+export LLVM_VERSION=21
 cd ./xeus-cpp
 mkdir build
 cd build
diff --git a/README.md b/README.md
index e14a94d94..6976c9b1e 100644
--- a/README.md
+++ b/README.md
@@ -104,10 +104,10 @@ git clone --depth=1 https://github.com/compiler-research/cppyy-backend.git
 
 #### Setup Clang-REPL
 
-Clone the 20.x release of the LLVM project repository.
+Clone the 21.x release of the LLVM project repository.
 
 ```bash
-git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
 cd llvm-project
 ```
 
@@ -406,10 +406,10 @@ git clone --depth=1 https://github.com/compiler-research/cppyy-backend.git
 
 #### Setup Clang-REPL
 
-Clone the 20.x release of the LLVM project repository.
+Clone the 21.x release of the LLVM project repository.
 
 ```bash
-git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
 cd llvm-project
 ```
 
diff --git a/docs/DevelopersDocumentation.rst b/docs/DevelopersDocumentation.rst
index e586cc5d8..a440e05c6 100644
--- a/docs/DevelopersDocumentation.rst
+++ b/docs/DevelopersDocumentation.rst
@@ -34,11 +34,11 @@ library
  Setup Clang-REPL
 ******************
 
-Clone the 20.x release of the LLVM project repository.
+Clone the 21.x release of the LLVM project repository.
 
 .. code:: bash
 
-   git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+   git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
    cd llvm-project
 
 ******************
diff --git a/docs/Emscripten-build-instructions.rst b/docs/Emscripten-build-instructions.rst
index 89e9be0d2..87de691ac 100644
--- a/docs/Emscripten-build-instructions.rst
+++ b/docs/Emscripten-build-instructions.rst
@@ -57,7 +57,7 @@ and on Windows execute in Powershell
    $env:PWD_DIR= $PWD.Path
    $env:SYSROOT_PATH="$env:EMSDK/upstream/emscripten/cache/sysroot"
 
-Now clone the 20.x release of the LLVM project repository and CppInterOp
+Now clone the 21.x release of the LLVM project repository and CppInterOp
 (the building of the emscripten version of llvm can be avoided by
 executing micromamba install llvm -c
 <https://repo.mamba.pm/emscripten-forge> and setting the LLVM_BUILD_DIR/$env:LLVM_BUILD_DIR
@@ -65,7 +65,7 @@ appropriately)
 
 .. code:: bash
 
-   git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+   git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
    git clone --depth=1 https://github.com/compiler-research/CppInterOp.git
 
 Now move into the cloned llvm-project folder and apply the required patches. On Linux and osx this
@@ -74,16 +74,16 @@ executing
 .. code:: bash
 
    cd ./llvm-project/
-   git apply -v ../CppInterOp/patches/llvm/emscripten-clang20-*.patch
+   git apply -v ../CppInterOp/patches/llvm/emscripten-clang21-*.patch
 
 On Windows execute the following
 
 .. code:: powershell
 
    cd .\llvm-project\
-   cp -r ..\patches\llvm\emscripten-clang20*
-   git apply -v emscripten-clang20-2-shift-temporary-files-to-tmp-dir.patch
-   git apply -v emscripten-clang20-3-enable_exception_handling.patch
+   cp -r ..\patches\llvm\emscripten-clang21*
+   git apply -v emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch
+   git apply -v emscripten-clang21-2-enable_exception_handling.patch
 
 We are now in a position to build an emscripten build of llvm by executing the following on Linux
 and osx
@@ -365,7 +365,7 @@ build folder, you can build the wasm version of xeus-cpp by executing
 
    cd ../..
    git clone --depth=1 https://github.com/compiler-research/xeus-cpp.git
-   export LLVM_VERSION=20
+   export LLVM_VERSION=21
    cd ./xeus-cpp
    mkdir build
    cd build
diff --git a/docs/InstallationAndUsage.rst b/docs/InstallationAndUsage.rst
index 3ec6470b4..526e32882 100644
--- a/docs/InstallationAndUsage.rst
+++ b/docs/InstallationAndUsage.rst
@@ -34,11 +34,11 @@ library
  Setup Clang-REPL
 ******************
 
-Clone the 20.x release of the LLVM project repository.
+Clone the 21.x release of the LLVM project repository.
 
 .. code:: bash
 
-   git clone --depth=1 --branch release/20.x https://github.com/llvm/llvm-project.git
+   git clone --depth=1 --branch release/21.x https://github.com/llvm/llvm-project.git
    cd llvm-project
 
 ******************
diff --git a/docs/ReleaseNotes.md b/docs/ReleaseNotes.md
index 811519dea..a39ef6220 100644
--- a/docs/ReleaseNotes.md
+++ b/docs/ReleaseNotes.md
@@ -25,7 +25,7 @@ infrastructure are described first.
 ## External Dependencies
 
 - CppInterOp now works with:
-  - llvm20
+  - llvm21
 
 ## Introspection
 
diff --git a/lib/CppInterOp/Compatibility.h b/lib/CppInterOp/Compatibility.h
index 24c822dec..1e9477c7e 100644
--- a/lib/CppInterOp/Compatibility.h
+++ b/lib/CppInterOp/Compatibility.h
@@ -31,6 +31,23 @@ static inline char* GetEnv(const char* Var_Name) {
 #endif
 }
 
+#if CLANG_VERSION_MAJOR < 21
+#define Print_Canonical_Types PrintCanonicalTypes
+#else
+#define Print_Canonical_Types PrintAsCanonical
+#endif
+
+#if CLANG_VERSION_MAJOR < 21
+#define clang_LookupResult_Found clang::LookupResult::Found
+#define clang_LookupResult_Not_Found clang::LookupResult::NotFound
+#define clang_LookupResult_Found_Overloaded clang::LookupResult::FoundOverloaded
+#else
+#define clang_LookupResult_Found clang::LookupResultKind::Found
+#define clang_LookupResult_Not_Found clang::LookupResultKind::NotFound
+#define clang_LookupResult_Found_Overloaded                                    \
+  clang::LookupResultKind::FoundOverloaded
+#endif
+
 #if CLANG_VERSION_MAJOR < 19
 #define Template_Deduction_Result Sema::TemplateDeductionResult
 #define Template_Deduction_Result_Success                                      \
@@ -412,11 +429,14 @@ inline void InstantiateClassTemplateSpecialization(
 #if CLANG_VERSION_MAJOR < 20
   interp.getSema().InstantiateClassTemplateSpecialization(
       clang::SourceLocation::getFromRawEncoding(1), CTSD,
-      clang::TemplateSpecializationKind::TSK_Undeclared, /*Complain=*/true);
+
+      clang::TemplateSpecializationKind::TSK_ExplicitInstantiationDefinition,
+      /*Complain=*/true);
 #else
   interp.getSema().InstantiateClassTemplateSpecialization(
       clang::SourceLocation::getFromRawEncoding(1), CTSD,
-      clang::TemplateSpecializationKind::TSK_Undeclared, /*Complain=*/true,
+      clang::TemplateSpecializationKind::TSK_ExplicitInstantiationDefinition,
+      /*Complain=*/true,
       /*PrimaryHasMatchedPackOnParmToNonPackOnArg=*/false);
 #endif
 }
diff --git a/lib/CppInterOp/CppInterOp.cpp b/lib/CppInterOp/CppInterOp.cpp
index f1527b4a8..0290dbe01 100755
--- a/lib/CppInterOp/CppInterOp.cpp
+++ b/lib/CppInterOp/CppInterOp.cpp
@@ -1307,16 +1307,16 @@ bool GetClassTemplatedMethods(const std::string& name, TCppScope_t parent,
   auto* DC = clang::Decl::castToDeclContext(D);
   Cpp_utils::Lookup::Named(&S, R, DC);
 
-  if (R.getResultKind() == clang::LookupResult::NotFound && funcs.empty())
+  if (R.getResultKind() == clang_LookupResult_Not_Found && funcs.empty())
     return false;
 
   // Distinct match, single Decl
-  else if (R.getResultKind() == clang::LookupResult::Found) {
+  else if (R.getResultKind() == clang_LookupResult_Found) {
     if (IsTemplatedFunction(R.getFoundDecl()))
       funcs.push_back(R.getFoundDecl());
   }
   // Loop over overload set
-  else if (R.getResultKind() == clang::LookupResult::FoundOverloaded) {
+  else if (R.getResultKind() == clang_LookupResult_Found_Overloaded) {
     for (auto* Found : R)
       if (IsTemplatedFunction(Found))
         funcs.push_back(Found);
@@ -2108,7 +2108,7 @@ static void GetDeclName(const clang::Decl* D, ASTContext& Context,
   PrintingPolicy Policy(Context.getPrintingPolicy());
   Policy.SuppressTagKeyword = true;
   Policy.SuppressUnwrittenScope = true;
-  Policy.PrintCanonicalTypes = true;
+  Policy.Print_Canonical_Types = true;
   if (const TypeDecl* TD = dyn_cast<TypeDecl>(D)) {
     // This is a class, struct, or union member.
     QualType QT;
diff --git a/lib/CppInterOp/exports.ld b/lib/CppInterOp/exports.ld
index e22490f2a..9d99a30c8 100644
--- a/lib/CppInterOp/exports.ld
+++ b/lib/CppInterOp/exports.ld
@@ -51,4 +51,6 @@
 -Wl,--export=_ZNK5clang12FunctionDecl12getNumParamsEv
 -Wl,--export=__clang_Interpreter_SetValueNoAlloc
 -Wl,--export=__clang_Interpreter_SetValueWithAlloc
+-Wl,--export=_ZN5clang11Interpreter6createENSt3__210unique_ptrINS_16CompilerInstanceENS1_14default_deleteIS3_EEEENS2_IN4llvm3orc12LLJITBuilderENS4_IS9_EEEE
+-Wl,--export=_ZNK5clang13CXXRecordDecl19isInjectedClassNameEv
 -Wl,--export=_ZN4llvm15SmallVectorBaseIjE8set_sizeEm
\ No newline at end of file
diff --git a/patches/llvm/emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch b/patches/llvm/emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch
new file mode 100644
index 000000000..32ac45c13
--- /dev/null
+++ b/patches/llvm/emscripten-clang21-1-shift-temporary-files-to-tmp-dir.patch
@@ -0,0 +1,15 @@
+diff --git a/clang/lib/Interpreter/Wasm.cpp b/clang/lib/Interpreter/Wasm.cpp
+index aa10b160ccf8..184867e2b55f 100644
+--- a/clang/lib/Interpreter/Wasm.cpp
++++ b/clang/lib/Interpreter/Wasm.cpp
+@@ -76,8 +76,8 @@ llvm::Error WasmIncrementalExecutor::addModule(PartialTranslationUnit &PTU) {
+   llvm::TargetMachine *TargetMachine = Target->createTargetMachine(
+       PTU.TheModule->getTargetTriple(), "", "", TO, llvm::Reloc::Model::PIC_);
+   PTU.TheModule->setDataLayout(TargetMachine->createDataLayout());
+-  std::string ObjectFileName = PTU.TheModule->getName().str() + ".o";
+-  std::string BinaryFileName = PTU.TheModule->getName().str() + ".wasm";
++  std::string ObjectFileName = "/tmp/" + PTU.TheModule->getName().str() + ".o";
++  std::string BinaryFileName = "/tmp/" + PTU.TheModule->getName().str() + ".wasm";
+ 
+   std::error_code Error;
+   llvm::raw_fd_ostream ObjectFileOutput(llvm::StringRef(ObjectFileName), Error);