In May 2012, Fowler won the Wells Fargo Championship in Charlotte on the first extra hole of a sudden-death playoff. Replaying the 18th hole, he defeated Rory McIlroy and D. A. Points with a birdie to gain his first PGA Tour win. Fowler shot a 69 (−3) in the final round to finish in a three-way tie after 72 holes at Quail Hollow Club. This win enabled Fowler to break the top-25 in the world, placing him at number 24. The following week at The Players Championship in Ponte Vedra Beach, Florida, Fowler played the final hole at −11 under par and had a birdie opportunity to bring him within one of leader and eventual winner Matt Kuchar. Fowler, however, pushed his putt to the right and finished in a tie for second, the fifth second-place finish of his career.
PGA Championship: Finished T3 and two strokes behind McIlroy at the PGA Championship in his 20th major championship start, with T19 in 2013 the previous-best finish in four prior PGA Championship starts. Became the first to claim top-five finishes in all four majors since Woods in 2005. Since 1934, is just the third player to perform the feat, joining Woods in 2000 and 2005 and Jack Nicklaus in 1971 and 1973. Played all four majors in 32-under, with McIlroy second on the list, at 27-under.
Masters Tournament: Finished runner-up at the Masters, one stroke behind Patrick Reed, for his best result at the event. For the first time in eight starts at Augusta National, recorded four par-or-better rounds (70-72-65-67). Earned his third runner-up in a major (2nd/2018 Masters Tournament, T2/2014 The Open Championship, T2/2014 U.S. Open) and third top-five in the last four (2nd/2018 Masters Tournament, T5/2017 Open Championship, T5/2017 U.S. Open). With third-round 65, was one of just four players to post a bogey-free round during the week (Rory McIlroy/65, Jon Rahm/65, Si Woo Kim/65) with all four occurring in the final round.
Wells Fargo Championship: Made birdie-3 on the first extra hole (No. 18) to defeat Rory McIlroy and D.A. Points at the Wells Fargo Championship for his first TOUR win. Improved to 1-1 in playoffs (lost to Troy Matteson, 2009 Frys.com Open). The playoff was the fifth at the Wells Fargo Championship. At the age of 23 years, 4 months, 23 days, became the third player to make the Wells Fargo Championship his first PGA TOUR win (Anthony Kim in 2008 and McIlroy in 2010). Became the third-youngest winner of the event, behind McIlroy (20 years, 11 months, 28 days) and Kim (22, 10, 15). His win came in his 72nd start on TOUR and was his 16th top-10 finish. Opening-round 66 is the lowest start by a winner of the Wells Fargo Championship. Won in his third start at the Wells Fargo Championship (T6 in 2010 and T16 in 2011).
On August 26, 2018, he won The Northern Trust for his first playoff victory; in the process, he established a new record for the tournament when held at the Ridgewood Country Club, with a score of 266, besting the old Ridgewood record of 270, which was set in 2014 by Hunter Mahan. The following week, he won at the Dell Technologies Championship played at TPC Boston in Norton, Massachusetts, with a final score of −16, two shots clear of Justin Rose. This put him over 2000 points ahead of the second place player, Dustin Johnson, in the FedEx Cup rankings. This margin secured him top seeding at The Tour Championship, regardless of his finish at the BMW Championship. This also marked his fourth win on tour, third for the year, and second during the playoffs. At the Tour Championship, DeChambeau finished 19th out of 30 participants. As a result, he fell to 3rd in the FedEx Cup, winning $2,000,000.
Hyundai Tournament of Champions: Finished T6 in a Monday-start-Tuesday-finish event, the season-opening, 54-hole Hyundai Tournament of Champions. The event "started" twice during the regularly scheduled first round Friday and later Sunday, but both times PGA TOUR rules staff halted play due to unplayable windy conditions and subsequently voided all scores that had taken place. As the first player off the tee, he ended up hitting three "opening" shots of the season.