Preheat oven to 375°F. Cook macaroni 2 minutes less than package directions. Drain and set aside.
Melt butter in a large saucepan over medium heat. Whisk in flour and cook 1-2 minutes until golden.
Gradually whisk in warm milk and cream, cooking until sauce thickens, about 5 minutes. Remove from heat.
Stir in cheddar, Gruyère, Parmesan, mustard powder, garlic powder, salt, and pepper until smooth.
Combine sauce with pasta and pour into a greased 9x13 baking dish.
Top with buttered panko breadcrumbs and bake 25-30 minutes until golden and bubbling.