Preheat oven to 350°F. Line a baking sheet with parchment paper or lightly grease a 9x5-inch loaf pan.
In a large bowl, combine ground beef, crushed crackers, diced onion, beaten eggs, milk, salt, pepper, garlic powder, and 1/4 cup ketchup. Mix gently with your hands until just combined, being careful not to overmix.
Shape the mixture into a loaf and place on the prepared baking sheet or press into the loaf pan.
In a small bowl, whisk together remaining 1/2 cup ketchup, brown sugar, and mustard. Spread this glaze evenly over the top of the meatloaf.
Bake for 55-65 minutes until internal temperature reaches 160°F and the top is caramelized.
Remove from oven and let rest for 10 minutes before slicing and serving.