Kisner was born in Aiken, South Carolina. He played college golf at the University of Georgia and was a member of their 2005 NCAA Division I Championship team along with Chris Kirk, Richard Scott, and Brendon Todd. After graduating in 2006, he turned professional.
Kisner played on the mini-tours (NGA Hooters Tour and Tarheel Tour) from 2007 to 2009, winning three times. He also played in six Nationwide Tour events in 2009. He played the Nationwide Tour full-time in 2010, winning once at the Mylan Classic. He finished the year 11th on the money list and earned his 2011 PGA Tour card.
Kisner failed to earn enough money on the PGA Tour in 2011 to retain his card (181st on money list), but finished T-11 at qualifying school to earn his card for 2012. He again failed to retain his card, finishing 167th on the money list, and missed earning a card in qualifying school by one stroke. He returned to (the now renamed) Web.com Tour in 2013 and won the Chile Classic in March. He finished 13th on the 2013 Web.com Tour regular season money list to earn his 2014 PGA Tour card.
In 2014, Kisner finished sixth at the Wells Fargo Championship, eighth at the Wyndham Championship and ninth at the RBC Canadian Open.
During the 2015 PGA Tour, Kisner finished runner-up three times, losing all three in sudden-death playoffs. He was defeated at the 2015 RBC Heritage after losing on the second hole of the playoff to Jim Furyk. Kisner would go on to finish tied with Sergio García and Rickie Fowler at The Players Championship event in May after 72 holes, losing to Fowler on the first hole of sudden-death after the two remained tied following a three-hole aggregate playoff. At the Greenbrier Classic he again tied for second after losing a sudden-death playoff, which was eventually won by Danny Lee. Kisner was eliminated on the first extra hole with birdie. Other notable results were finishes for fourth at the McGladrey Classic, fifth at the Crowne Plaza Invitational at Colonial, and eighth at the Memorial Tournament.
Kisner finished as runner-up at the WGC-HSBC Champions event in Shanghai in November 2015, two strokes behind Russell Knox despite holding the 36-hole lead. This was Kisner's fourth runner-up finish of the 2015 calendar year.
On November 22, 2015, after a number of near misses, Kisner earned his first PGA Tour victory by winning the RSM Classic, in his 109th PGA Tour start. He won by six strokes over Kevin Chappell as he dominated the tournament over the weekend. He began the final round with a three stroke advantage and shot a final round of 64 to storm to his first victory. The win moved him into the Top 20 in the world rankings and put him at the top of the early FedEx Cup standings moving into 2016.
On May 28, 2017, Kisner won his second PGA Tour title at the Dean & DeLuca Invitational.
PGA Tour playoff record (0–4)2007 Tarheel Tour Match Play (Tarheel Tour)
2008 Bermuda Run Open (Tarheel Tour), Savannah Lakes Resort Classic (NGA Hooters Tour)
2013 Callaway Pebble Beach Invitational
CUT = missed the half-way cutMost consecutive cuts made – 8 (2016 Masters – 2017 PGA Championship, current)
Longest streak of top-10s – 1
"T" indicates a tie for a place
DNP = Did not play
QF, R16, R32, R64 = Round in which player lost in match play
"T" = tied
Yellow background for top-10.
ProfessionalPresidents Cup: 2017