diff --git a/browser/app/firefox.exe.manifest b/browser/app/firefox.exe.manifest
index 1e1d6f651d27..995b2fc869c1 100644
--- a/browser/app/firefox.exe.manifest
+++ b/browser/app/firefox.exe.manifest
@@ -36,12 +36,6 @@
     </ms_asmv3:requestedPrivileges>
   </ms_asmv3:security>
 </ms_asmv3:trustInfo>
-  <ms_asmv3:application xmlns:ms_asmv3="urn:schemas-microsoft-com:asm.v3">
-    <ms_asmv3:windowsSettings xmlns="http://schemas.microsoft.com/SMI/2005/WindowsSettings">
-      <dpiAware>True/PM</dpiAware>
-      <dpiAwareness xmlns="http://schemas.microsoft.com/SMI/2016/WindowsSettings">PerMonitorV2,PerMonitor</dpiAwareness>
-    </ms_asmv3:windowsSettings>
-  </ms_asmv3:application>
   <compatibility xmlns="urn:schemas-microsoft-com:compatibility.v1">
     <application>
       <supportedOS Id="{8e0f7a12-bfb3-4fe8-b9a5-48fd50a15a9a}"/>
diff --git a/browser/app/nsBrowserApp.cpp b/browser/app/nsBrowserApp.cpp
index 12ed20d3b00d..a755eeab080b 100644
--- a/browser/app/nsBrowserApp.cpp
+++ b/browser/app/nsBrowserApp.cpp
@@ -28,6 +28,7 @@
 #  include "freestanding/SharedSection.h"
 #  include "LauncherProcessWin.h"
 #  include "mozilla/WindowsDllBlocklist.h"
+#  include "mozilla/WindowsDpiInitialization.h"
 
 #  define XRE_WANT_ENVIRON
 #  define strcasecmp _stricmp
@@ -296,6 +297,19 @@ int main(int argc, char* argv[], char* envp[]) {
     DllBlocklist_Initialize(gBlocklistInitFlags |
                             eDllBlocklistInitFlagIsChildProcess);
 #  endif
+#  if defined(XP_WIN)
+    // Ideally, we would be able to set our DPI awareness in
+    // firefox.exe.manifest Unfortunately, that would cause Win32k calls when
+    // user32.dll gets loaded, which would be incompatible with Win32k Lockdown
+    //
+    // MSDN says that it's allowed-but-not-recommended to initialize DPI
+    // programatically, as long as it's done before any HWNDs are created.
+    // Thus, we do it almost as soon as we possibly can
+    {
+      auto result = mozilla::WindowsDpiInitialization();
+      (void)result;  // Ignore errors since some tools block DPI calls
+    }
+#  endif
 #  if defined(XP_WIN) && defined(MOZ_SANDBOX)
     // We need to initialize the sandbox TargetServices before InitXPCOMGlue
     // because we might need the sandbox broker to give access to some files.
@@ -328,6 +342,19 @@ int main(int argc, char* argv[], char* envp[]) {
 #endif
 
 #if defined(XP_WIN)
+
+  // Ideally, we would be able to set our DPI awareness in firefox.exe.manifest
+  // Unfortunately, that would cause Win32k calls when user32.dll gets loaded,
+  // which would be incompatible with Win32k Lockdown
+  //
+  // MSDN says that it's allowed-but-not-recommended to initialize DPI
+  // programatically, as long as it's done before any HWNDs are created.
+  // Thus, we do it almost as soon as we possibly can
+  {
+    auto result = mozilla::WindowsDpiInitialization();
+    (void)result;  // Ignore errors since some tools block DPI calls
+  }
+
   // Once the browser process hits the main function, we no longer need
   // a writable section handle because all dependent modules have been
   // loaded.
diff --git a/mozglue/misc/WindowsDpiInitialization.cpp b/mozglue/misc/WindowsDpiInitialization.cpp
new file mode 100644
index 000000000000..2e957b583012
--- /dev/null
+++ b/mozglue/misc/WindowsDpiInitialization.cpp
@@ -0,0 +1,73 @@
+/* This Source Code Form is subject to the terms of the Mozilla Public
+ * License, v. 2.0. If a copy of the MPL was not distributed with this
+ * file, You can obtain one at http://mozilla.org/MPL/2.0/. */
+
+#include "mozilla/WindowsDpiInitialization.h"
+
+#include "mozilla/DynamicallyLinkedFunctionPtr.h"
+#include "mozilla/WindowsProcessMitigations.h"
+#include "mozilla/WindowsVersion.h"
+
+#include <shellscalingapi.h>
+#include <windows.h>
+
+namespace mozilla {
+
+typedef HRESULT(WINAPI* SetProcessDpiAwarenessType)(PROCESS_DPI_AWARENESS);
+typedef BOOL(WINAPI* SetProcessDpiAwarenessContextType)(DPI_AWARENESS_CONTEXT);
+
+WindowsDpiInitializationResult WindowsDpiInitialization() {
+  // DPI Awareness can't be used in a Win32k Lockdown process, so there's
+  // nothing to do
+  if (IsWin32kLockedDown()) {
+    return WindowsDpiInitializationResult::Success;
+  }
+
+  // From MSDN:
+  //  SetProcessDpiAwarenessContext() was added in the Win10 Anniversary Update
+  //  SetProcessDpiAwareness() was added in Windows 8.1
+  //  SetProcessDpiAware() was added in Windows Vista
+  //
+  //  DPI_AWARENESS_CONTEXT_PER_MONITOR_AWARE_V2 wasn't added later until
+  //  the Creators Update, so if it fails we just fall back to
+  //  DPI_AWARENESS_CONTEXT_PER_MONITOR_AWARE
+  if (IsWin10AnniversaryUpdateOrLater()) {
+    DynamicallyLinkedFunctionPtr<SetProcessDpiAwarenessContextType>
+        setProcessDpiAwarenessContext(L"user32.dll",
+                                      "SetProcessDpiAwarenessContext");
+    if (!setProcessDpiAwarenessContext) {
+      return WindowsDpiInitializationResult::
+          FindSetProcessDpiAwarenessContextFailed;
+    }
+
+    if (!setProcessDpiAwarenessContext(
+            DPI_AWARENESS_CONTEXT_PER_MONITOR_AWARE_V2) &&
+        !setProcessDpiAwarenessContext(
+            DPI_AWARENESS_CONTEXT_PER_MONITOR_AWARE)) {
+      return WindowsDpiInitializationResult::
+          SetProcessDpiAwarenessContextFailed;
+    }
+
+    return WindowsDpiInitializationResult::Success;
+  } else if (IsWin8Point1OrLater()) {
+    DynamicallyLinkedFunctionPtr<SetProcessDpiAwarenessType>
+        setProcessDpiAwareness(L"Shcore.dll", "SetProcessDpiAwareness");
+    if (!setProcessDpiAwareness) {
+      return WindowsDpiInitializationResult::FindSetProcessDpiAwarenessFailed;
+    }
+
+    if (FAILED(setProcessDpiAwareness(PROCESS_PER_MONITOR_DPI_AWARE))) {
+      return WindowsDpiInitializationResult::SetProcessDpiAwarenessFailed;
+    }
+
+    return WindowsDpiInitializationResult::Success;
+  } else {
+    if (!SetProcessDPIAware()) {
+      return WindowsDpiInitializationResult::SetProcessDPIAwareFailed;
+    }
+
+    return WindowsDpiInitializationResult::Success;
+  }
+}
+
+}  // namespace mozilla
diff --git a/mozglue/misc/WindowsDpiInitialization.h b/mozglue/misc/WindowsDpiInitialization.h
new file mode 100644
index 000000000000..5943d50526e3
--- /dev/null
+++ b/mozglue/misc/WindowsDpiInitialization.h
@@ -0,0 +1,54 @@
+/* -*- Mode: C++; tab-width: 4; indent-tabs-mode: nil; c-basic-offset: 2 -*- */
+/* This Source Code Form is subject to the terms of the Mozilla Public
+ * License, v. 2.0. If a copy of the MPL was not distributed with this
+ * file, You can obtain one at http://mozilla.org/MPL/2.0/. */
+
+#ifndef MOZILLA_MOZGLUE_MISC_WINDOWSDPIINITIALIZATION_H_
+#define MOZILLA_MOZGLUE_MISC_WINDOWSDPIINITIALIZATION_H_
+#include "mozilla/Types.h"
+
+namespace mozilla {
+
+// The result codes that may be returned from WindowsDpiInitialization()
+enum class WindowsDpiInitializationResult : uint32_t {
+  Success,
+  FindSetProcessDpiAwarenessContextFailed,
+  SetProcessDpiAwarenessContextFailed,
+  FindSetProcessDpiAwarenessFailed,
+  SetProcessDpiAwarenessFailed,
+  SetProcessDPIAwareFailed,
+};
+
+// Get a string representation of any WindowsDpiInitializationResult value
+inline const char* WindowsDpiInitializationResultString(
+    WindowsDpiInitializationResult result) {
+  switch (result) {
+    case WindowsDpiInitializationResult::Success:
+      return "Success";
+    case WindowsDpiInitializationResult::
+        FindSetProcessDpiAwarenessContextFailed:
+      return "Failed to find SetProcessDpiAwarenessContext";
+    case WindowsDpiInitializationResult::SetProcessDpiAwarenessContextFailed:
+      return "SetProcessDpiAwarenessContext failed";
+    case WindowsDpiInitializationResult::FindSetProcessDpiAwarenessFailed:
+      return "Failed to find SetProcessDpiAwareness";
+    case WindowsDpiInitializationResult::SetProcessDpiAwarenessFailed:
+      return "SetProcessDpiAwareness failed";
+    case WindowsDpiInitializationResult::SetProcessDPIAwareFailed:
+      return "SetProcessDPIAware failed";
+    default:
+      return "Unknown result";
+  }
+}
+
+// Initialize DPI awareness to the best available for the current OS
+// According to MSDN, this will be:
+// Per-Monitor V2 for Windows 10 Creators Update (1703) and later
+// Per-Monitor V1 for Windows 8.1 and later
+// System DPI for Vista and later (we don't support anything older)
+// https://docs.microsoft.com/en-us/windows/win32/hidpi/high-dpi-desktop-application-development-on-windows
+MFBT_API WindowsDpiInitializationResult WindowsDpiInitialization();
+
+}  // namespace mozilla
+
+#endif  // MOZILLA_MOZGLUE_MISC_WINDOWSDPIINITIALIZATION_H_
diff --git a/mozglue/misc/moz.build b/mozglue/misc/moz.build
index 45c2a7773ecf..36e472d6918a 100644
--- a/mozglue/misc/moz.build
+++ b/mozglue/misc/moz.build
@@ -59,6 +59,7 @@ if CONFIG["OS_ARCH"] == "WINNT":
         "DynamicallyLinkedFunctionPtr.h",
         "ImportDir.h",
         "NativeNt.h",
+        "WindowsDpiInitialization.h",
         "WindowsEnumProcessModules.h",
         "WindowsMapRemoteView.h",
         "WindowsProcessMitigations.h",
@@ -69,6 +70,7 @@ if CONFIG["OS_ARCH"] == "WINNT":
     SOURCES += [
         "PreXULSkeletonUI.cpp",
         "TimeStamp_windows.cpp",
+        "WindowsDpiInitialization.cpp",
         "WindowsMapRemoteView.cpp",
         "WindowsProcessMitigations.cpp",
         "WindowsUnicode.cpp",