Prep the oven: Preheat the oven to 375°F (190°C). Grease a 9 × 13-inch baking dish.
Cook the pasta: Boil the macaroni in salted water until slightly under al dente, about 5–6 minutes depending on the brand. Drain and set aside.
Make the roux: Melt 8 tablespoons of butter in a large saucepan over medium heat. Whisk in the flour and cook for 1–2 minutes, stirring constantly, until bubbly and the raw flour smell fades.
Add the liquids: Gradually whisk in the milk and heavy cream. Simmer for 3–5 minutes, stirring until the sauce thickens enough to coat a spoon.
Season the sauce: Stir in the garlic powder, onion powder, ground mustard, salt, black pepper, and cayenne.
Add the cheese: Remove the saucepan from the heat. Gradually stir in 3 cups of the shredded cheese mixture (2¼ cups sharp cheddar and ¾ cup Gruyère) until melted and smooth. Reserve the remaining 1 cup (¾ cup sharp cheddar and ¼ cup Gruyère) for layering.
Combine: Fold the cooked macaroni into the sauce until evenly coated.
Layer: Spread half the macaroni mixture in the baking dish. Add ½ cup of the reserved cheese, then spread the remaining macaroni mixture over it. Sprinkle the remaining ½ cup of cheese on top.
Prepare the topping: Mix the Panko breadcrumbs with the remaining 2 tablespoons of melted butter. Scatter evenly over the dish.
Bake: Bake uncovered for 20–25 minutes, until bubbling around the edges and golden on top.
Rest and serve: Let stand for 10 minutes before serving.
