Busch led the last 40 laps at the Infineon Raceway and was in front 78 laps overall.
The win was the ninth of Busch's Sprint Cup career. It gave him a 103-point lead over Jeff Burton in the cup standings.
Busch twice made pit stops prior to a caution flag, helping him keep the lead. He praised his pit crew.
"These guys worked so hard," he said. "This is really special. We came a long ways with this thing. That's what makes me so proud of this team."
Jeff Gordon, Bowyer and Casey Mears finished 3-4-5.
The next race is June 29 at the New Hampshire International Speedway.
Millions of Getty images now available for free via embed tool
Aaron Carter is still in love with Hilary Duff