Gather all ingredients and arrange them next to a small mixing bowl to ensure nothing is missed.

In the mixing bowl, whisk together mustard powder, garlic powder, black pepper, and salt until evenly combined.

Add ketchup, brown sugar, apple cider vinegar, and Worcestershire sauce to the bowl and stir with a whisk or fork until the sugar is fully dissolved and the sauce is smooth.

Check the consistency; if the sauce is too thick to spread easily, whisk in water 1 teaspoon at a time until it coats the back of a spoon.

Taste the sauce and adjust sweetness or tang by adding more brown sugar or vinegar as desired.

Brush or spoon half of the sauce evenly over the top of the prepared meatloaf in a loaf pan.

Bake the meatloaf with the first layer of sauce at 350°F (175°C) for 25 to 30 minutes until the sauce begins to caramelize.

Remove the meatloaf from the oven and spread the remaining sauce over the top, covering any dry spots.

Return the meatloaf to the oven and bake for an additional 20 to 30 minutes, or until the internal temperature reaches 160°F (71°C) for beef or pork, or 165°F (74°C) for turkey.