Boil a large pot of salted water and cook the whole wheat macaroni according to package directions until al dente.
While pasta cooks, steam the butternut squash cubes until fork-tender, approximately 10 to 12 minutes.
Place the steamed squash and milk into a high-speed blender and process until completely smooth and creamy.
Transfer the squash puree to a large saucepan over medium-low heat.
Add the shredded cheddar cheese to the squash puree, whisking constantly until the cheese is fully melted and the sauce is uniform.
Remove the saucepan from the heat and whisk in the Greek yogurt, garlic powder, onion powder, paprika, salt, and pepper.
Drain the cooked pasta and return it to its original pot.
Pour the cheese sauce over the pasta and fold gently until every noodle is thoroughly coated.
Serve immediately while warm.