In a large bowl combine sharp cheddar, monterey jack, and smoked gruyere.
In a medium bowl combine salt, black pepper, onion powder, garlic powder, dry mustard, smoked paprika, and cayenne pepper. Mix until combined and set aside.
Preheat oven to 375°F. Heat a large 5 quart pot over medium heat, add butter, once butter is melted stir in flour and mix with a whisk until a blonde roux is formed.
Sprinkle in 1 teaspoon of the seasoning mix, then slowly pour in the whole milk, while stirring to prevent any lumps. Stir in heavy cream, seasoning mix and a third of the cheese blend, cook for 3-5 minutes constantly stirring until cheese melts and sauce is smooth and thick enough to coat a spoon.
Stir in macaroni until the cheese sauce coats the pasta.
Pour half the macaroni into a 9 x 13 baking dish then evenly sprinkle half the brisket, then a third of the cheese.
Then repeat for the final layer. Bake in the oven for 22-25 minutes until the cheese is melted and slightly bubbling around the edges.
Cool for 10 minutes before serving and serve immediately.