Kisner, who will rise from his current position of 50th in the world rankings thanks to his first World Golf Championships title, reached the final at Austin Country Club in 2018, only to be thumped 7 and 6 by Bubba Watson.
The tone for that contest was set by Watson winning each of the first five holes, but Kisner was never behind on this occasion as he overcame Kuchar in a somewhat underwhelming decider.
Neither player was at their best on Sunday afternoon in Texas, perhaps unsurprisingly given they were each playing their fourth round in two days and seventh of the week. Both men were also taken the full 18 in their morning semi-finals, Kisner edging out Francesco Molinari and Kuchar getting the better of Lucas Bjerregaard.
Kisner birdied the opening hole of the final to move one up and was two to the good through seven holes as his opponent struggled badly on the greens.
A three-putt from Kisner at the ninth enabled Kuchar to reduce his arrears, but the 2013 champion then found water on the par-three 11th to slip back to two down.
When Kuchar made a sloppy bogey at 15, Kisner was three up with three to play and on the brink of the biggest victory of his career.
He sealed victory in style, converting a 20-foot birdie putt at the 16th after an eagle attempt from Kuchar had come up agonisingly short.
Ryder Cup star Molinari eased past Bjerregaard in the consolation match, the Italian triumphing 4 and 2.
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