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 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 approximately 3/4 inch thick. Bake for 20 minutes, then remove from the oven and drain any excess fat.
04 - While the meatloaf layer bakes, cook the elbow macaroni in a large pot of salted boiling water 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 enough to coat the back of a spoon.
06 - Remove the saucepan from heat and stir in the shredded cheddar, grated Parmesan, dry mustard, smoked paprika, salt, and pepper. Stir until all the cheese has melted and the sauce is smooth. Fold in the cooked macaroni until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the parbaked meatloaf layer, pressing gently to create a level surface.
08 - In a small bowl, combine the shredded cheddar, 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 squares. Serve hot.