Heat the oven to 350°F and line a rimmed sheet pan with parchment.
Mix the breadcrumbs and milk in a large bowl and let them stand for 5 minutes.
Add the beef, eggs, onion, Worcestershire, salt, pepper and 1/4 cup ketchup and mix gently just until combined.
Shape the mixture into a 9-by-5-inch loaf on the pan, keeping the sides straight but not packing it hard.
Stir the remaining ketchup with the brown sugar and vinegar, spread it over the loaf, and bake for 60 to 70 minutes until the center reaches 160°F.
Rest for 15 minutes before slicing so the juices stay in the meat instead of flooding the pan.