Preheat the oven to 350°F (175°C).
Cook the macaroni according to package instructions until al dente. Drain and set aside.
Steam the butternut squash until tender, about 15 minutes.
Melt butter in a saucepan over medium heat, then whisk in flour to form a roux.
Gradually whisk in the milk until the mixture is smooth and beginning to thicken.
Stir in garlic powder, onion powder, salt, and pepper, then mix in the cheddar and Parmesan cheeses until melted.
In a blender, combine the cooked butternut squash with a small amount of the cheese sauce until smooth.
Combine the macaroni with the cheese sauce and the blended squash until fully coated.
Transfer the mixture to a greased baking dish and top with breadcrumbs, if using.
Bake for 20-25 minutes until the top is golden and the mixture is bubbling.
Let rest for a few minutes before serving hot.