The No. 18 Joe Gibbs Racing Toyota driver held off points leader Clint Bowyer at the finish to win for the fourth time this season and the ninth time in his Nationwide career.
Hamlin also gave JGR its 17th Nationwide victory this season.
"We didn't have the best race car at the beginning, but we did some great adjustments during the race, and we just came on there in the second part," Hamlin said.
David Ragan, Carl Edwards and Matt Kenseth completed the top-five finishers.
Kevin Harvick, who started on the pole and led 88 of the first 93 laps, settled for a 13th-place finish.
With five races left in the 2008 season, Bowyer holds a 196-point lead over second-place Carl Edwards and a 268-point advantage over third-place Brad Keselowski, who finished sixth.