He finished with a six-under round at the Seaside course at Sea Island for a tournament record 22-under-par 260 total.
American Kevin Chappell shot 67 to take second place on 16-under 266, one stroke better than Northern Irishman Graeme McDowell, who also returned a 67 on St Simons Island.
"I was just playing so well all year, I knew that one day it was going to happen where I would make all the putts on Sunday and I did it today on the front nine," said Kisner, who was greeted on the final green by his baby daughter Kate.
"I hope it's just opening the bucket and the flood gates are open. You got to believe you can win on Thursday and I hope this catapults me into believing that every week."
Kisner became the sixth first-time winner since the beginning of the new season this autumn after logging four runner-up finishes over the last seven months, the latest coming two weeks ago at the WGC-HSBC Champions in Shanghai.
His near misses included three playoff losses in a 12-week span, including a loss to Rickie Fowler in extra holes at The Players Championship.
This victory was never in doubt as the American, who recently bought a vacation home in the seaside resort area, never let anyone closer than three shots as he cruised to victory.
(Reporting by Larry Fine in New York; Editing by Ken Ferris)
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