Melt the butter in a large pot over medium heat. Add the flour, garlic powder, onion powder, and smoked paprika. Cook, stirring, for 2 minutes.
Whisk in the milk and bring the mixture to a simmer. Cook for 5 minutes, stirring occasionally, until the sauce is thickened.
Meanwhile, cook the macaroni in a large pot of boiling salted water until al dente, stirring occasionally. Drain and set aside.
Add the cream cheese, 1 1/2 cups of cheddar cheese, Parmesan cheese, and black pepper to the sauce. Cook, stirring, until the cheese is melted and the sauce is creamy.
Add the cooked macaroni to the sauce and stir to combine. Transfer the mac and cheese to the slow cooker and top with the remaining 1/2 cup of cheddar cheese.
Cover and cook on low for 2-3 hours, or until the cheese is melted and the mac and cheese is hot and bubbly.
Sprinkle with the bread crumbs and serve.