diff --git a/src/dawn/native/RenderPipeline.cpp b/src/dawn/native/RenderPipeline.cpp
index 1830b10ca8..364c645b38 100644
--- a/src/dawn/native/RenderPipeline.cpp
+++ b/src/dawn/native/RenderPipeline.cpp
@@ -326,7 +326,8 @@ MaybeError ValidateColorTargetState(
 
 MaybeError ValidateFragmentState(DeviceBase* device,
                                  const FragmentState* descriptor,
-                                 const PipelineLayoutBase* layout) {
+                                 const PipelineLayoutBase* layout,
+                                 bool alphaToCoverageEnabled) {
     DAWN_INVALID_IF(descriptor->nextInChain != nullptr, "nextInChain must be nullptr.");
 
     DAWN_TRY_CONTEXT(ValidateProgrammableStage(device, descriptor->module, descriptor->entryPoint,
@@ -357,6 +358,11 @@ MaybeError ValidateFragmentState(DeviceBase* device,
         }
     }
 
+    DAWN_INVALID_IF(fragmentMetadata.usesSampleMaskOutput && alphaToCoverageEnabled,
+                    "alphaToCoverageEnabled is true when the sample_mask builtin is a "
+                    "pipeline output of fragment stage of %s.",
+                    descriptor->module);
+
     return {};
 }
 
@@ -447,7 +453,8 @@ MaybeError ValidateRenderPipelineDescriptor(DeviceBase* device,
                      "validating multisample state.");
 
     if (descriptor->fragment != nullptr) {
-        DAWN_TRY_CONTEXT(ValidateFragmentState(device, descriptor->fragment, descriptor->layout),
+        DAWN_TRY_CONTEXT(ValidateFragmentState(device, descriptor->fragment, descriptor->layout,
+                                               descriptor->multisample.alphaToCoverageEnabled),
                          "validating fragment state.");
 
         DAWN_INVALID_IF(descriptor->fragment->targetCount == 0 && !descriptor->depthStencil,
diff --git a/src/dawn/native/ShaderModule.cpp b/src/dawn/native/ShaderModule.cpp
index a1e96ac269..206869f407 100644
--- a/src/dawn/native/ShaderModule.cpp
+++ b/src/dawn/native/ShaderModule.cpp
@@ -773,6 +773,7 @@ ResultOrError<std::unique_ptr<EntryPointMetadata>> ReflectEntryPointUsingTint(
         if (entryPoint.input_sample_mask_used) {
             totalInterStageShaderComponents += 1;
         }
+        metadata->usesSampleMaskOutput = entryPoint.output_sample_mask_used;
         if (entryPoint.sample_index_used) {
             totalInterStageShaderComponents += 1;
         }
diff --git a/src/dawn/native/ShaderModule.h b/src/dawn/native/ShaderModule.h
index 1df775cfba..a491a2141b 100644
--- a/src/dawn/native/ShaderModule.h
+++ b/src/dawn/native/ShaderModule.h
@@ -249,6 +249,8 @@ struct EntryPointMetadata {
     std::unordered_set<std::string> initializedOverridableConstants;
 
     bool usesNumWorkgroups = false;
+    // Used at render pipeline validation.
+    bool usesSampleMaskOutput = false;
 };
 
 class ShaderModuleBase : public ApiObjectBase, public CachedObject {
diff --git a/src/dawn/tests/unittests/validation/RenderPipelineValidationTests.cpp b/src/dawn/tests/unittests/validation/RenderPipelineValidationTests.cpp
index bc47381c34..4e265a2797 100644
--- a/src/dawn/tests/unittests/validation/RenderPipelineValidationTests.cpp
+++ b/src/dawn/tests/unittests/validation/RenderPipelineValidationTests.cpp
@@ -768,6 +768,56 @@ TEST_F(RenderPipelineValidationTest, AlphaToCoverageAndSampleCount) {
     }
 }
 
+// Tests if the sample_mask builtin is a pipeline output of fragment shader,
+// then alphaToCoverageEnabled must be false
+TEST_F(RenderPipelineValidationTest, AlphaToCoverageAndSampleMaskOutput) {
+    wgpu::ShaderModule fsModuleSampleMaskOutput = utils::CreateShaderModule(device, R"(
+        struct Output {
+            @builtin(sample_mask) mask_out: u32,
+            @location(0) color : vec4<f32>,
+        }
+        @fragment fn main() -> Output {
+            var o: Output;
+            // We need to make sure this sample_mask isn't optimized out even its value equals "no op".
+            o.mask_out = 0xFFFFFFFFu;
+            o.color = vec4<f32>(1.0, 1.0, 1.0, 1.0);
+            return o;
+        }
+    )");
+
+    {
+        utils::ComboRenderPipelineDescriptor descriptor;
+        descriptor.vertex.module = vsModule;
+        descriptor.cFragment.module = fsModuleSampleMaskOutput;
+        descriptor.multisample.count = 4;
+        descriptor.multisample.alphaToCoverageEnabled = false;
+
+        device.CreateRenderPipeline(&descriptor);
+    }
+
+    {
+        utils::ComboRenderPipelineDescriptor descriptor;
+        descriptor.vertex.module = vsModule;
+        descriptor.cFragment.module = fsModuleSampleMaskOutput;
+        descriptor.multisample.count = 4;
+        descriptor.multisample.alphaToCoverageEnabled = true;
+
+        ASSERT_DEVICE_ERROR(device.CreateRenderPipeline(&descriptor));
+    }
+
+    {
+        // Control cases: when fragment has no sample_mask output, it's good to have
+        // alphaToCoverageEnabled enabled
+        utils::ComboRenderPipelineDescriptor descriptor;
+        descriptor.vertex.module = vsModule;
+        descriptor.cFragment.module = fsModule;
+        descriptor.multisample.count = 4;
+        descriptor.multisample.alphaToCoverageEnabled = true;
+
+        device.CreateRenderPipeline(&descriptor);
+    }
+}
+
 // Tests that the texture component type in shader must match the bind group layout.
 TEST_F(RenderPipelineValidationTest, TextureComponentTypeCompatibility) {
     constexpr uint32_t kNumTextureComponentType = 3u;