Preheat oven to 375°F and line a baking sheet with parchment paper.
Cook macaroni until al dente, drain and set aside. Make cheese sauce by melting butter, whisking in flour, then milk until thickened, and stirring in 2 cups cheddar cheese until smooth. Mix with macaroni and let cool slightly.
In a large bowl, combine ground beef, breadcrumbs, eggs, milk, onion, garlic, Worcestershire sauce, 1 teaspoon salt, 1/2 teaspoon pepper, and 1/4 cup ketchup, mixing until just combined.
On the prepared baking sheet, pat half the meat mixture into a 10x8 inch rectangle.
Spoon the mac and cheese down the center lengthwise, leaving 2 inches on each side, and sprinkle with remaining 1/2 cup cheddar cheese.
Place remaining meat mixture on top and seal the edges completely, shaping into a loaf.
Mix remaining 1/4 cup ketchup with paprika and brush over the top of the meatloaf.
Bake for 55-60 minutes until internal temperature reaches 160°F, then let rest for 10 minutes before slicing to serve.