Fold two long sheets of heavy-duty foil into strips and cross them in a 6-quart slow cooker, leaving handles above the rim.
Mix the beef, crackers, onion, eggs, milk, Worcestershire, salt, pepper and 1/4 cup ketchup just until evenly combined.
Shape the mixture into an 8-by-4-inch loaf and set it on the foil sling without pressing it against the crock.
Whisk the remaining ketchup, brown sugar and mustard and brush half of it over the loaf.
Cover and cook on low until the center reaches 150°F, 3 1/2 to 4 hours.
Brush on the remaining glaze, cover and continue cooking until the center reaches 160°F, 20 to 30 minutes.
Turn off the cooker, rest the loaf for 15 minutes and use the foil handles to lift it to a board.
Blot any fat from the edges and cut into thick slices.