Preheat the oven to 375°F and lightly grease a baking dish so the finished bake releases cleanly and slices easily.
Bring a large pot of salted water to a rolling boil. Cook the pasta until just al dente so it holds its texture during baking. Drain thoroughly and set aside.
In a large bowl, gently mix the ground beef, breadcrumbs, milk, eggs, garlic, onion, and Italian seasoning just until combined. Avoid overmixing to keep the meatloaf tender.
Press the meatloaf mixture evenly into the prepared baking dish, forming a flat layer without compacting it too tightly.
Bake the meatloaf layer for about 25 minutes so it sets and releases excess fat before adding the pasta layer.
While the meatloaf bakes, melt butter in a saucepan over medium heat. Whisk in flour and cook briefly to remove the raw flour taste.
Slowly whisk in warmed milk, stirring constantly until the sauce thickens and becomes smooth and creamy.
Lower the heat and stir in the shredded cheeses until fully melted. Season lightly with salt and pepper.
Add the cooked pasta to the cheese sauce and stir gently so each piece is evenly coated.
Remove the baking dish from the oven and carefully spread the mac and cheese evenly over the partially baked meatloaf.
Return the casserole to the oven and bake for 25 minutes, until bubbly and lightly golden.
Let the bake rest for at least 10 minutes before serving so the layers set and portions hold together.