Combine turkey, onion, garlic, egg, breadcrumbs, onion powder, and ketchup in a bowl and mix together using a fork until well combined.
In a large pot, heat sauce over medium-low heat. While sauce is heating, roll meat mixture into 1” in diameter balls. Carefully place meatballs in hot sauce and simmer, covered, until cooked through, about 12 minutes.
Meanwhile, bring 4-6 quarts of water to a boil and cook penne pasta according to package directions.
Once pasta is tender, reserve 1 cup of pasta water and drain pasta. Combine pasta with sauce and meatballs in pot, add ½ cup of pasta water and cook 1-2 minutes.