Tear bread into large pieces and blend in a food processor until they form fine crumbs. Combine crumbs, sirloin, mushrooms, mozzarella, pepperoni, oregano, garlic, salt and eggs in a large bowl and mix gently with your hands to combine. Form mixture into a 9-inch-by-6-inch loaf. Place in slow cooker.
Brush meatloaf with ketchup, cover, and cook on low until meat is cooked through, about 5 hours.