Preheat the oven: Preheat your oven to 350°F (175°C). Grease a 9×13-inch baking dish or use a cast-iron skillet for extra flavor.
- Prepare the pasta: Bring a large pot of salted water to a boil and cook the macaroni according to the package instructions, about 7-8 minutes, until al dente. Drain and set aside.
- Make the cheese sauce: In a large saucepan, melt the butter over medium heat. Add the flour and whisk constantly for 1-2 minutes to create a roux. Gradually whisk in the milk and cream, continuing to stir until the sauce thickens and becomes smooth, about 5-7 minutes. Lower the heat and stir in the cheddar, mozzarella, and Parmesan cheeses until melted and smooth. Season with garlic powder, onion powder, salt, and pepper. Taste and adjust as needed.
- Assemble the mac and cheese: Add the drained pasta to the cheese sauce and stir to combine, making sure all the pasta is coated in the sauce. Transfer to the prepared baking dish.
- Prepare the topping: In a small bowl, combine the panko breadcrumbs, melted butter, and grated Parmesan. Stir until the breadcrumbs are well coated.
- Top and bake: Sprinkle the breadcrumb mixture evenly over the mac and cheese. Bake in the preheated oven for 25-30 minutes, or until the top is golden brown and the sauce is bubbly. If you prefer a crispier topping, broil for an additional 2-3 minutes.
- Serve: Let the mac and cheese cool for 5-10 minutes before serving. Serve warm and enjoy!