diff --git a/goldens/public-api/core/errors.api.md b/goldens/public-api/core/errors.api.md
index 4f575ac92e8..9832a074115 100644
--- a/goldens/public-api/core/errors.api.md
+++ b/goldens/public-api/core/errors.api.md
@@ -79,6 +79,8 @@ export const enum RuntimeErrorCode {
     // (undocumented)
     INVALID_MULTI_PROVIDER = -209,
     // (undocumented)
+    INVALID_SET_INPUT_CALL = 317,
+    // (undocumented)
     INVALID_SKIP_HYDRATION_HOST = -504,
     // (undocumented)
     LOOP_TRACK_DUPLICATE_KEYS = -955,
diff --git a/packages/core/src/errors.ts b/packages/core/src/errors.ts
index ff71b1d956a..afeda548b34 100644
--- a/packages/core/src/errors.ts
+++ b/packages/core/src/errors.ts
@@ -62,6 +62,7 @@ export const enum RuntimeErrorCode {
   UNINITIALIZED_LET_ACCESS = 314,
   NO_BINDING_TARGET = 315,
   INVALID_BINDING_TARGET = 316,
+  INVALID_SET_INPUT_CALL = 317,
 
   // Bootstrap Errors
   MULTIPLE_PLATFORMS = 400,
diff --git a/packages/core/src/render3/component_ref.ts b/packages/core/src/render3/component_ref.ts
index a01d501b9e3..aab486edd64 100644
--- a/packages/core/src/render3/component_ref.ts
+++ b/packages/core/src/render3/component_ref.ts
@@ -260,6 +260,9 @@ export class ComponentFactory<T> extends AbstractComponentFactory<T> {
             rootViewInjector,
           )
         : createHostElement(cmpDef, hostRenderer);
+      const hasInputBindings =
+        componentBindings?.some(isInputBinding) ||
+        directives?.some((d) => typeof d !== 'function' && d.bindings.some(isInputBinding));
 
       const rootLView = createLView<T>(
         null,
@@ -355,7 +358,7 @@ export class ComponentFactory<T> extends AbstractComponentFactory<T> {
         leaveView();
       }
 
-      return new ComponentRef(this.componentType, rootLView);
+      return new ComponentRef(this.componentType, rootLView, !!hasInputBindings);
     } finally {
       setActiveConsumer(prevConsumer);
     }
@@ -454,6 +457,10 @@ function getRootTViewTemplate(
   };
 }
 
+function isInputBinding(binding: Binding): boolean {
+  return binding[BINDING].kind === 'input';
+}
+
 /**
  * Represents an instance of a Component created via a {@link ComponentFactory}.
  *
@@ -473,7 +480,8 @@ export class ComponentRef<T> extends AbstractComponentRef<T> {
 
   constructor(
     componentType: Type<T>,
-    private _rootLView: LView,
+    private readonly _rootLView: LView,
+    private readonly _hasInputBindings: boolean,
   ) {
     super();
     this._tNode = getTNode(_rootLView[TVIEW], HEADER_OFFSET) as TElementNode;
@@ -487,6 +495,13 @@ export class ComponentRef<T> extends AbstractComponentRef<T> {
   }
 
   override setInput(name: string, value: unknown): void {
+    if (this._hasInputBindings && ngDevMode) {
+      throw new RuntimeError(
+        RuntimeErrorCode.INVALID_SET_INPUT_CALL,
+        'Cannot call `setInput` on a component that is using the `inputBinding` function.',
+      );
+    }
+
     const tNode = this._tNode;
     this.previousInputValues ??= new Map();
     // Do not set the input if it is the same as the last value
diff --git a/packages/core/test/acceptance/create_component_spec.ts b/packages/core/test/acceptance/create_component_spec.ts
index 14d05ca1099..66d4c48d4da 100644
--- a/packages/core/test/acceptance/create_component_spec.ts
+++ b/packages/core/test/acceptance/create_component_spec.ts
@@ -1084,6 +1084,28 @@ describe('createComponent', () => {
         ref.changeDetectorRef.detectChanges();
       }).toThrowError(/RootDir does not have an input with a public name of "someInput"/);
     });
+
+    it('should throw when using setInput on a component already using inputBindings', () => {
+      @Component({template: ''})
+      class RootComp {
+        @Input() someInput = '';
+      }
+
+      const hostElement = document.createElement('div');
+      const environmentInjector = TestBed.inject(EnvironmentInjector);
+      const ref = createComponent(RootComp, {
+        hostElement,
+        environmentInjector,
+        bindings: [inputBinding('someInput', () => 'hello')],
+      });
+      ref.changeDetectorRef.detectChanges();
+
+      expect(() => {
+        ref.setInput('someInput', 'changed');
+      }).toThrowError(
+        /Cannot call `setInput` on a component that is using the `inputBinding` function/,
+      );
+    });
   });
 
   describe('error checking', () => {