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Preheat oven to 375°F (190°C). Lightly grease a 9x9-inch or similar baking dish.
In a bowl, mix ground beef, egg, breadcrumbs, milk, ketchup, Worcestershire, garlic powder, onion powder, salt, and pepper. Press the mixture evenly into the bottom of the baking dish to form the meatloaf base.
Bake uncovered for 20–25 minutes until the meat is nearly cooked through. Drain any excess fat if needed.
Meanwhile, cook the macaroni in salted water until just al dente. Drain and set aside.
In a saucepan, melt butter over medium heat. Whisk in flour and cook 1 minute. Slowly add milk, whisking constantly, until smooth. Simmer until thickened, 3–4 minutes.
Stir in cheddar cheese, mustard powder, salt, and pepper. Once melted, add the drained pasta and stir to coat.
Pour mac and cheese over the baked meatloaf layer. Smooth the top, then sprinkle with extra cheese and crushed crackers if using. Drizzle with melted butter.
Return to oven and bake for another 15–20 minutes until golden and bubbly.
Let rest 5–10 minutes before slicing and serving.