Busch was tied with Sam Ard for the previous record with 10 wins. Busch also won 10 races in 2008, matching the record Ard set in NASCAR's second-tier series in 1983.
Busch is closing in on Mark Martin's career Nationwide mark of 48 wins. Busch is in second at 41.
He led 192 of 200 laps, received a big ovation after the race and waved his index finger out the window.
"It's very cool," Busch said. "We've still got more races to go. I'm looking forward to more wins hopefully."
Joey Logano was second and Carl Edwards third.
Danica Patrick ran into the wall early in the race and was forced into the garage. She returned in the No. 7 Chevrolet and finished 94 laps down in 35th place.
"It's hot out there. I just took a nice little break in the middle 100 laps," Patrick said. "No, I was really disappointed."
Busch wasn't disappointed with another stellar outing on the 1-mile concrete track. He also has three wins in Sprint Cup and five in the Trucks Series this season. He became the first driver in the 15 years that NASCAR has been running three national series to win all of them in the same week when he did it last month at Bristol Motor Speedway.
About the only time Busch didn't dominate Dover was during a 10 minute, 42-second red flag caused by a vicious accident that took out Drew Herring and Elliott Sadler. Debris, oil and fluid covered the track after the scary wreck. Both drivers walked away fine.
Busch has 18 top-fives this season running a partial schedule in the No. 11 Toyota for Joe Gibbs Racing.