The second of two late-race restarts came just after Hamlin had entered the final lap, triggered when Kevin Harvick bumped Joey Logano to put Logano into a spin.
Hamlin quickly lengthened his lead as the race resumed, holding off Tony Stewart and Joe Gibbs teammate Kyle Busch to take the Gillette Fusion ProGlide 500 and extend his Sprint Cup-best 2010 championship total to four.
Busch passed Stewart to gain second place with only one lap to go, giving the Gibbs team a 1-2 finish at the unique 2.5-mile triangular track.
Sprint Cup points leader Kevin Harvick ended in fourth place and Jimmie Johnson rounded out the Top 5.
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