Preheat your oven to 375°F. Lightly grease a 9x13 baking dish.
Boil the macaroni just shy of al dente, about 1 minute less than package directions. Drain and set aside.
In a large pot over medium heat, melt butter. Whisk in flour and cook for 1 minute, stirring constantly.
Slowly add the milk and cream, whisking to smooth out lumps. Cook until it starts to thicken—5 to 6 minutes.
Lower the heat and stir in cheddar and mozzarella until melted and smooth. Add salt, pepper, garlic, and onion powder.
Add the drained pasta to the cheese sauce and stir to coat evenly.
Pour into the prepared baking dish. Mix panko with melted butter and sprinkle over the top (if using).
Bake for 25–30 minutes, until the top is golden and bubbling. Cool for 10 minutes before diving in.