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Bring a large pot of salted water to a boil. Cook macaroni in boiling water uncovered, stirring occasionally, until tender yet firm to the bite, about 8 minutes; drain.
Preheat the oven to 350 degrees F (175 degrees C). Grease a 9x13-inch baking dish with cooking spray.
Melt butter in a large skillet over medium-high heat. Cook and stir ham and onion in hot butter until onion is tender, about 5 minutes. Stir in garlic and cook for about 2 minutes more; remove the skillet from heat.
Add macaroni, Cheddar cheese, condensed soup, peas, milk, sour cream, onion powder, and garlic powder to ham mixture in the skillet; mix until well combined. Transfer mixture to the prepared baking dish.
Bake in the preheated oven until cheese is melted, about 25 minutes. Sprinkle French-fried onions over casserole and continue baking until golden, about 5 minutes more.