Preheat oven to 375°F; line a baking sheet with parchment.
Cook macaroni al dente; drain and set aside. Melt butter, whisk in flour, then milk until thickened; stir in 2 cups cheddar until smooth. Mix with macaroni; cool slightly.
Mix beef, breadcrumbs, eggs, milk, onion, garlic, Worcestershire, 1 teaspoon salt, 1/2 teaspoon pepper, and 1/4 cup ketchup in a large bowl just until combined.
Pat half the meat mixture into a 10x8 inch rectangle on sheet.
Spoon macaroni down center lengthwise, leaving 2 inches each side; sprinkle with remaining 1/2 cup cheddar.
Top with remaining meat; seal edges completely and shape into loaf.
Mix remaining 1/4 cup ketchup and paprika; brush over loaf.
Bake 55-60 minutes until internal temperature reaches 160°F; rest 10 minutes before slicing and serving.