Hamlin -- a rookie who was the pole-sitter -- captured a checkered flag for the first time in his career.
He led 49 of the first 50 laps before the flat tire dropped him to 40th during pit crew repairs.
"We're trying to get into the (Nextel Cup) Chase and this is a great way to do it," Hamlin said.
During a late surge, Hamlin held off all challengers, including teammate Tony Stewart, on the final five laps.
Jeff Gordon wrecked his car after a brake failure and did not finish. He was knocked out of the top 10 in the point standings.
"That was one of the hardest hits I've ever taken," Gordon said.
In the points chase, Jimmy Johnson has 2,145 to 2,097 for Kenseth.