Heat grill to 350º. Trim fat cap of brisket so there’s just a thin, even layer.

Combine 2 tablespoons each onion powder, garlic powder, sugar, mustard powder, chili powder, and 2 teaspoons salt in a small bowl. Rub evenly over the entire surface of the meat. Let sit at room temperature, uncovered, for 20 minutes.

Place the brisket fat-cap-side down over a direct flame and cook until spices are browned, about 10 minutes. Flip and grill the other side for about another 10 minutes.

Adjust grill heat to 250º. Move brisket to the grill's cool zone and close the lid. After 2 hours, insert an instant-read thermometer into the thickest part of the meat. When it reads 180º, transfer the brisket to a large piece of foil and replace it on the grill. Crimp the edges up slightly so it will catch the juices from the meat as it finishes cooking.

Close the grill and continue cooking until the meat reaches 200°, 45 minutes to 1 hour more.

Transfer to a cutting board and tent with aluminum foil. Let rest 30 minutes.

In a medium microwave-safe bowl, combine the ketchup, Worcestershire sauce, remaining tablespoon each onion powder, garlic powder, sugar, mustard powder, chili powder, the apple cider vinegar, and 1 teaspoon salt. Microwave until warm, about 1 minute. Stir in any juices that collected in the foil, if you like.

Slice the meat against the grain and serve with the sauce.