Preheat the oven to 350°F (175°C). Line a rimmed baking sheet with foil and lightly grease it, or lightly grease a 9×5-inch loaf pan. A free-form loaf on a sheet pan gives you delicious caramelized edges all around.
Make the panade: in a large bowl, stir together the breadcrumbs and milk and let them sit for 5 minutes until the breadcrumbs soak up the milk and turn soft and mushy. This is the secret to a juicy meatloaf — never skip it.
Mix the meatloaf: add the ground beef, diced onion, eggs, 1/4 cup ketchup, Worcestershire sauce, garlic powder, onion powder, salt, pepper, and parsley to the bowl. Using clean hands, mix gently until everything is just combined. Do not overmix — overmixing makes meatloaf dense and tough.
Shape the loaf: transfer the mixture to the prepared baking sheet and shape it into an even loaf about 9 inches long and 4 inches wide, smoothing the top and sides.
Make the glaze: in a small bowl, whisk together the 1/2 cup ketchup, brown sugar, apple cider vinegar, and mustard. Spread half of the glaze evenly over the top and sides of the meatloaf.
Bake: bake for 50 minutes. Remove from the oven, spread the remaining glaze over the top, and return to the oven for 15 to 20 minutes more, until the glaze is bubbly and caramelized and the internal temperature reads 160°F (71°C).
Rest and serve: let the meatloaf rest for 10 to 15 minutes before slicing — this lets the juices redistribute so every slice stays moist. Slice thick and serve warm.