01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or nonstick spray.
02 - In a large mixing bowl, combine ground beef, diced onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and 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 about ¾ inch thick. Bake for 20 minutes until partially set.
04 - While the meatloaf layer bakes, cook elbow macaroni according to package directions until just al dente. Drain well and set aside.
05 - In a medium saucepan over medium heat, melt butter. Whisk in flour and cook for 1 minute to form a roux. Slowly pour in milk while whisking constantly. Continue cooking and whisking for 2 to 3 minutes until the sauce thickens enough to coat the back of a spoon.
06 - Remove saucepan from heat and stir in shredded cheddar, grated Parmesan, dry mustard, paprika, salt, and pepper. Stir until all cheese is melted and the sauce is smooth. Fold in the drained macaroni until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the par-baked meatloaf layer, covering it completely to the edges.
08 - In a small bowl, combine shredded cheddar, panko breadcrumbs, and melted butter. Mix until the breadcrumbs are evenly moistened. Sprinkle the topping uniformly over the casserole.
09 - Return the assembled casserole to the oven and bake for 30 to 35 minutes until the top is golden brown and bubbling, and the meatloaf layer is fully cooked through to an internal temperature of 160°F.
10 - Remove from oven and let the casserole rest for 10 minutes before slicing into squares. Serve hot.