01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or non-stick spray.
02 - In a large mixing bowl, combine the ground beef, chopped onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and black pepper. Mix gently with your hands until just combined, being careful not to overwork the meat.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish, creating a uniform layer. Bake for 20 minutes until partially cooked through.
04 - While the meatloaf bakes, cook the elbow macaroni according to package directions until just al dente. Drain well and set aside.
05 - In a medium saucepan over medium heat, melt the butter. Whisk in the flour and cook for 1 minute to form a roux. Slowly pour in the whole milk while whisking constantly, and continue cooking for 2 to 3 minutes until the sauce thickens slightly.
06 - Stir the shredded cheddar, grated Parmesan, dry mustard, paprika, salt, and pepper into the sauce. Stir until the cheeses are fully melted and the sauce is smooth. Fold in the cooked macaroni until evenly coated.
07 - Remove the par-baked meatloaf from the oven. Carefully drain off any excess grease. Spread the macaroni and cheese mixture evenly over the meatloaf layer.
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 assembled 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.