Season the brisket on both sides with ½ teaspoon kosher salt and ¼ teaspoon black pepper.
In a large Dutch oven, heat the oil over medium-high heat.
Add the brisket to the pot and sear until golden brown; flip and repeat.
Remove from heat and add the onions.
In a glass measuring cup or bowl, whisk to combine the ketchup, stock, garlic, brown sugar, paprika, white vinegar, and the remaining 1 teaspoon salt and ¼ teaspoon black pepper.
Pour the sauce over the brisket to coat.
Cover and bake for 2 ½–3 hours, or until the brisket is tender. Set aside.
Bring a large pot of salted water to a boil over high heat.
Add the pasta and cook until almost al dente.
Drain and rinse with cold water to stop the cooking process. Set aside.
In a large pot, melt the butter.
Transfer 2 tablespoons of the melted butter into a bowl and toss with the panko to coat. Set aside.
Add the flour to the remaining butter in the pot. Cook, whisking, until the color deepens, 1–2 minutes.
Slowly add the milk, whisking until smooth with each addition until all of the milk has been added.
Continue to cook over medium heat, whisking, until the mixture is slightly thickened and coats the back of a spoon.
Remove from heat. Add the cheeses, salt, and pepper, and whisk until smooth.
Add the drained pasta to the pot and stir to coat with the cheese sauce.
Preheat the oven to 425 F.
Lightly grease a 5-quart baking dish.
Pour the pasta mixture evenly into the dish.
Top with the panko mixture.
Bake for 20–25 minutes, until golden brown.
While the mac and cheese is baking, transfer the brisket to a cutting board, reserving the sauce in a bowl.
Thinly slice the brisket, and then chop it into bite-sized pieces.
Stir the brisket back into the sauce.
Pour the brisket over the baked mac and cheese, then garnish with chopped parsley.