• Cook the pasta. Bring a large pot of salted water to a boil. Cook the pasta 2 minutes less than the package directions for al dente. Drain well and set aside.
• Get ready to bake. Preheat the oven to 375°F. Lightly grease a 9×13-inch baking dish.
• Make the béchamel sauce. Melt the butter in a large saucepan over medium heat. Whisk in the flour and cook for about 1 minute, stirring constantly. Gradually whisk in the milk until smooth. Cook for 3–5 minutes, whisking frequently, until the mixture is slightly thickened.
• Make the butternut squash cheese sauce. Reduce the heat to low. Whisk in the butternut squash purée, cream cheese, Dijon mustard, garlic powder, smoked paprika, and nutmeg until smooth. Remove from the heat. Gradually stir in the cheddar, mozzarella, and Parmesan until melted and smooth. Season with salt and black pepper to taste.
• Combine. Add the cooked pasta to the cheese sauce and stir until evenly coated. Transfer the mixture to the prepared baking dish and spread evenly.
• Add the topping. In a small bowl, combine the panko breadcrumbs, melted butter, and Parmesan cheese. Sprinkle evenly over the mac and cheese.
• Bake. Bake uncovered for 20–25 minutes, until hot and bubbling and the topping is golden brown. Let rest for 5 minutes before serving.

Make Butternut Squash Puree From Scratch

• Prep. Preheat the oven to 425°F and line a baking sheet with parchment paper.
• Prepare the squash and roast. Cut 1 medium butternut squash in half lengthwise and scoop out the seeds and stringy pulp. Place the squash halves, cut-side down, on the prepared baking sheet. Roast for 40–50 minutes, or until the flesh is completely tender and easily pierced with a fork.
• Scoop and puree. Let the squash cool slightly. Scoop the flesh from the skin and transfer it to a food processor or blender. Blend until completely smooth.
• Measure. Measure 1 cup of purée for the mac and cheese. If the purée seems very watery, let it drain briefly through a fine-mesh strainer before using.