diff --git a/mlir/cmake/modules/AddMLIRPython.cmake b/mlir/cmake/modules/AddMLIRPython.cmake
--- a/mlir/cmake/modules/AddMLIRPython.cmake
+++ b/mlir/cmake/modules/AddMLIRPython.cmake
@@ -547,6 +547,19 @@
       $<$<PLATFORM_ID:Linux>:LINKER:--exclude-libs,ALL>
   )
 
+  if(WIN32)
+    # On Windows, pyconfig.h (and by extension python.h) hardcode the version of the
+    # python library which will be used for linkage depending on the flavor of the build.
+    # pybind11 has a workaround which depends on the definition of Py_DEBUG (if Py_DEBUG
+    # is not passed in as a compile definition, pybind11 undefs _DEBUG when including
+    # python.h, so that the release python library would be used).
+    # Since mlir uses pybind11, we can leverage their workaround by never directly
+    # pyconfig.h or python.h and instead relying on the pybind11 headers to include the
+    # necessary python headers. This results in mlir always linking against the
+    # release python library via the (undocumented) cmake property Python3_LIBRARY_RELEASE.
+    target_link_libraries(${libname} PRIVATE ${Python3_LIBRARY_RELEASE})
+  endif()
+
   ################################################################################
   # Install
   ################################################################################
diff --git a/mlir/include/mlir-c/Bindings/Python/Interop.h b/mlir/include/mlir-c/Bindings/Python/Interop.h
--- a/mlir/include/mlir-c/Bindings/Python/Interop.h
+++ b/mlir/include/mlir-c/Bindings/Python/Interop.h
@@ -21,7 +21,14 @@
 #ifndef MLIR_C_BINDINGS_PYTHON_INTEROP_H
 #define MLIR_C_BINDINGS_PYTHON_INTEROP_H
 
-#include <Python.h>
+// We *should*, in theory, include Python.h here in order to import the correct
+// definitions for what we need below, however, importing Python.h directly on
+// Windows results in the enforcement of either pythonX.lib or pythonX_d.lib
+// depending on the build flavor. Instead, we rely on the fact that this file
+// (Interop.h) is always included AFTER pybind11 and will therefore have access
+// to the definitions from Python.h in addition to having a workaround applied
+// through the pybind11 headers that allows us to control which python library
+// is used.
 
 #include "mlir-c/AffineExpr.h"
 #include "mlir-c/AffineMap.h"
diff --git a/mlir/lib/Bindings/Python/ExecutionEngineModule.cpp b/mlir/lib/Bindings/Python/ExecutionEngineModule.cpp
--- a/mlir/lib/Bindings/Python/ExecutionEngineModule.cpp
+++ b/mlir/lib/Bindings/Python/ExecutionEngineModule.cpp
@@ -6,7 +6,6 @@
 //
 //===----------------------------------------------------------------------===//
 
-#include "mlir-c/Bindings/Python/Interop.h"
 #include "mlir-c/ExecutionEngine.h"
 #include "mlir/Bindings/Python/PybindAdaptors.h"
 
diff --git a/mlir/lib/Bindings/Python/IRCore.cpp b/mlir/lib/Bindings/Python/IRCore.cpp
--- a/mlir/lib/Bindings/Python/IRCore.cpp
+++ b/mlir/lib/Bindings/Python/IRCore.cpp
@@ -19,7 +19,6 @@
 #include "mlir-c/Registration.h"
 #include "llvm/ADT/ArrayRef.h"
 #include "llvm/ADT/SmallVector.h"
-#include <pybind11/stl.h>
 
 #include <utility>