Preheat the oven to 350°F (175°C).
Cook the elbow macaroni according to package instructions. Drain and set aside.
In a large pot, melt 1/4 cup butter over medium heat. Stir in the flour and cook for about 1 minute, until the mixture becomes slightly golden.
Gradually whisk in the milk, ensuring there are no lumps. Continue to cook until the sauce thickens, about 3-5 minutes.
Add the cheddar, mozzarella, and Parmesan cheeses to the sauce. Stir until the cheese has melted and the sauce is smooth.
Season the sauce with garlic powder, onion powder, salt, and pepper.
Add the cooked macaroni to the cheese sauce, stirring to coat evenly.
Transfer the mac and cheese mixture to a greased 9x13-inch baking dish.
In a small bowl, melt the 2 tbsp butter and mix it with the Panko breadcrumbs. Sprinkle the breadcrumb mixture evenly over the top of the mac and cheese.
Bake for 25-30 minutes, or until the top is golden and bubbly. Let cool for 5 minutes before serving.