Hamlin led for 91 laps in the Pocono Raceway event and took over the lead for good when he slipped by Clint Bowyer for the top position with 10 laps to go. He held off Juan Pablo Montoya by 0.870 seconds.
His most recent win had been in the 2008 spring event at Martinsville, Va.
It was Hamlin's fifth career Sprint Cup series victory and came after his grandmother died last week.
Bowyer finished third, Sam Hornish Jr. fourth and Kasey Kahne fifth.
Tony Stewart finished 10th and slightly increased his Cup lead to 197 points over Jimmie Johnson, who came in 13th.
Copyright 2009 by United Press International.
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