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 with a one-stroke victory over three other players. On March 25, 2018, Kisner finished runner-up in the
WGC-Dell Technologies Match Play in Austin, Texas. He lost to
Bubba Watson in the final, 7 & 6. He also tied for second with a score of six-under-par at the
2018 Open Championship. On March 31, 2019, Kisner once again reached the championship round of the
WGC-Dell Technologies Match Play. This time, he won the tournament (3 & 2) over fellow American
Matt Kuchar. In August 2021, Kisner won the
Wyndham Championship with a birdie on the second extra hole in a six-man sudden-death playoff. In September 2022, Kisner was selected for the U.S. team in the
2022 Presidents Cup; he tied one and lost two of the three matches he played. ==Charity==