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Preheat oven to 375°F.
Bring 4 quarts of salted water to a rolling boil in a large pot.
Add 1 pound elbow macaroni and cook 7–9 minutes until al dente; drain and set aside.
In a Dutch oven over medium heat, melt ½ cup unsalted butter.
Whisk in ½ cup all-purpose flour and cook 1–2 minutes to form a roux.
Gradually whisk in 4 cups whole milk until smooth, then whisk in 1 cup heavy cream.
Cook, whisking constantly, until sauce thickens and gently bubbles, about 5–7 minutes.
Remove from heat and stir in 2 cups shredded sharp cheddar, 2 cups shredded smoked Gouda, and 1 cup shredded Monterey Jack until melted.
Stir in 1 tablespoon smoked paprika, 1 teaspoon dry mustard powder, 1 teaspoon salt, and ½ teaspoon black pepper.
Optionally stir in ½ teaspoon liquid smoke for extra smoky flavor.
Fold drained macaroni into cheese sauce until evenly coated.
Transfer mixture to a 9×13-inch baking dish and sprinkle ½ cup Panko breadcrumbs over the top.
Bake 20–25 minutes until bubbly and golden brown.
Let rest 10 minutes before serving.