Varner turned professional in 2012, missing the cut at the Chiquita Classic. Prior to playing on the Web.com Tour, he played on the eGolf Professional Tour and Florida Tour. He qualified for the 2013 U.S. Open, but missed the cut.
Varner started playing on the Web.com Tour in 2014, making 13 cuts in 21 tournaments with two top-10 finishes. His best finish was T-2 at the Rex Hospital Open. He finished 30th on the money list in his first full season. He also played in two PGA Tour events, the Northern Trust Open (T70) and Wells Fargo Championship (missed cut).
In 2015, he had five top-25 finishes and a runner-up finish at the Panama Claro Championship. He finished 25th on the Web.com Tour regular season money list, the last guaranteed spot, to earn a PGA Tour card for the 2015–16 season. Varner is the first African-American golfer to advance to the PGA Tour via the Web.com Tour.
In December 2016, Varner earned his first professional golf victory by winning the Australian PGA Championship, a tournament co-sanctioned by the PGA Tour of Australasia and the European Tour.[3] He is only the second American to win the Australian PGA Championship and the first since Hale Irwin won it in 1978.[4] He also became the third black man to win on the European Tour after Vincent Tshabalala of South Africa and Tiger Woods.
In May 2019, Varner was tied for second heading into the final round of the PGA Championship on Bethpage Black outside of New York City. He played in the final group with eventual champion Brooks Koepka but shot 81 to finish tied for 36th.
In April 2021, Varner recorded his best finish to date on the PGA Tour. A tied-second place at the RBC Heritage; four shots behind Stewart Cink.[5]
In April 2022, Varner held his first solo 54-hole PGA Tour lead at the RBC Heritage. He finished tied for third, one shot behind winner Jordan Spieth. He moved to a career high 36th in the world rankings.[7] In May 2022 at the Charles Schwab Challenge, Varner was tied for the lead after the 11th hole in the final round. He finished the round 9 shots back of the eventual winner after closing at +10 over the final seven holes.[8] In August 2022, it was announced that Varner had joined LIV Golf.[9]