01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or nonstick cooking spray.
02 - In a large mixing bowl, combine the ground beef, diced onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and pepper. Mix gently with your hands until just combined — avoid overworking the meat to keep it tender.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish, creating a uniform flat layer. Bake for 20 minutes to partially cook the meatloaf base.
04 - While the meatloaf layer bakes, cook the elbow macaroni according to package directions until just al dente. Drain well and set aside.
05 - In a medium saucepan, melt the butter over medium heat. Whisk in the flour and cook for 1 minute to form a roux. Slowly pour in the whole milk while whisking constantly and cook for 2 to 3 minutes until the sauce thickens slightly.
06 - Stir the cheddar cheese, Parmesan cheese, dry mustard, paprika, salt, and pepper into the sauce. Continue stirring until the cheeses are fully melted and the sauce is smooth. Fold in the cooked macaroni and mix until evenly coated.
07 - Remove the par-baked meatloaf layer from the oven and drain any excess grease. Spread the macaroni and cheese mixture evenly over the meatloaf base.
08 - In a small bowl, combine the shredded cheddar cheese, panko breadcrumbs, and melted butter. Sprinkle the mixture evenly across the top of the casserole.
09 - Return the casserole to the oven and bake for 30 to 35 minutes until the topping is golden brown and the edges are bubbling.
10 - Remove from the oven and let the casserole rest for 10 minutes before slicing into portions. Serve hot.