Preheat oven to 375°F (190°C).
In a large mixing bowl, combine the ground beef, breadcrumbs, milk, egg, onion, garlic, oregano, salt, and pepper. Mix by hand until ingredients are evenly distributed, avoiding overworking the meat.
Place half of the meat mixture into a 9x5 inch loaf pan, forming a well in the center.
Place the mozzarella cheese block into the well.
Top with the remaining meat mixture, pinching the edges to seal the cheese completely inside.
In a small bowl, whisk together the ketchup, brown sugar, and mustard to create the glaze.
Spread half of the glaze over the top of the meatloaf.
Bake for 45 minutes in the preheated oven.
Spread the remaining glaze over the meatloaf and continue baking for 15 minutes, or until the internal temperature reaches 160°F (71°C).
Remove from oven and allow the meatloaf to rest for 10 minutes before slicing to ensure the cheese sets.