Preheat oven to 350 degrees F (175 degrees C).
In a large bowl, thoroughly mix ground beef, onion, salt, pepper and garlic powder. Mix in bread, milk, egg, 2 tablespoons mustard and 1/4 cup ketchup.
Press the meat mixture into a 9×5-inch loaf pan. In a small bowl, stir together remaining mustard, ketchup and brown sugar; pour on top of the meat loaf.
Bake in the preheated oven until an instant-read thermometer inserted into the center reads 165 degrees F (74 degrees C), about 2 hours.
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