Preheat the oven to 350°F (175°C).
Cook the elbow macaroni in a large pot of salted boiling water according to package instructions until al dente, about 8 minutes. Drain and set aside.
In a large skillet over medium heat, add the ground beef, salt, black pepper, garlic powder, and onion powder. Cook, breaking up the meat with a spoon, until browned and cooked through, about 7-8 minutes. Drain excess fat and set aside.
In a medium saucepan, melt the butter over medium heat. Whisk in the flour and cook for 1-2 minutes until lightly golden and bubbling.
Gradually whisk in the whole milk, continuing to whisk until the mixture thickens and starts to bubble, about 5-7 minutes.
Remove the saucepan from heat and stir in the shredded cheddar cheese, mozzarella cheese, Parmesan cheese, and dry mustard powder until the cheese is fully melted and the sauce is smooth.
In a large mixing bowl, combine the cooked macaroni, browned ground beef, and cheese sauce. Stir until evenly mixed.
Transfer the mixture to a greased 9×13-inch baking dish and spread evenly.
Bake in the preheated oven for 20 minutes until bubbly and the top is lightly golden.
Remove from the oven and let the casserole rest for 5 minutes before serving.