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: With his T5 finish at the PGA Championship, finishing three strokes behind champion Justin Thomas, continued to be a top-five machine in major championships, recording his seventh such finish in 32 starts. Made a furious Sunday rally, with six birdies, including four in a row on Nos 12-15, but pars on The Green Mile (Nos. 16-18) left him a few short of his friend, Justin Thomas.
On 27 January 2016, Lowry returned to Australia after a decade away from Australia when he signed a two-and-a-half-year deal with A-League side Perth Glory. Upon joining Perth Glory, Lowry said of the move, quoting: "I've got a lot of experience behind me now and I want to use it to guide the young lads who are in this young squad. I've spent 11 years in England and it's shaped my football over there and I'm really happy to be here and get stuck into the games"
Frys.com Open: At the Frys.com Open in Scottsdale, Ariz., reached a three-way playoff with Jamie Lovemark and eventual-winner Troy Matteson. Began the final round four strokes behind Matteson, but played his first five holes in 5-under, punctuated by a hole-in-one from 211 yards at the par-3 fifth hole. After finishing T2 in the playoff, he had recorded all eight of his professional rounds in the 60s. Thanks to the T7 in Las Vegas at the Justin Timberlake Shriners Hospitals for Children Open and T2 finish at Grayhawk GC, he surpassed No. 150 from the 2008 money list, earning special temporary membership on TOUR for the remainder of the season.
Lowry elected to turn professional the week after his Irish Open triumph, meaning that he would miss out on the opportunity to play in the Walker Cup in September 2009. He made his professional début on 28 May at the European Open, where he shot 78 in the first round to end the opening day almost at the back of the field, and went on to miss the cut following a second round 73.
After a T-12 finish at the Masters, Fowler earned his first win in over three years with a playoff victory at The Players Championship in May. Trailing Sergio García midway through the final round by five shots, Fowler played the final six holes in 6-under par, including an eagle at the par-5 16th. After a birdie at the famous 17th hole, Fowler's final birdie of the round on 18 left him at 12-under par. Both García and Kevin Kisner had birdie attempts to win at the 18th in regulation, but both missed and the three men went to a three-hole aggregate playoff to decide a winner on holes 16–18. Fowler and Kisner went par-birdie-par to tie at −1 while García's three pars left him at even and he was eliminated. Thus Fowler and Kisner went to sudden death starting at the 17th, where Kisner's tee shot landed within about 12 feet (3.7 m) of the cup. Fowler answered with a shot inside of five feet, and when Kisner's birdie attempt slid by, Fowler responded by making his short birdie to claim the championship. Fowler played his final 10 holes in 8-under par. On July 12, he won the Aberdeen Asset Management Scottish Open on the European Tour, shooting a 12-under-par 268. On September 7, he won the Deutsche Bank Championship, the second FedEx Cup Playoffs event, by one stroke over Henrik Stenson, for his third victory on the PGA Tour.
Shell Houston Open: After opening with an 8-under 64 for a one-stroke lead on day one, added rounds of 71-67-70 to finish T3 at the Shell Houston Open. Erased a seven-shot deficit in the third round and started the final round three shots behind 54-hole leader Sung Kang, but a final-round 70 saw him finish four strokes behind winner Russell Henley. With 27 birdies on the week (tied for most with Henley), marked his most birdies in a single event.
In June 2015, he became the first SMU Mustang to win the NCAA individual championship, recording a score of 280 (−8) to win by one stroke. In August, he won the U.S. Amateur title, defeating Derek Bard 7 & 6 in the 36-hole final. He became the fifth player to win both the NCAA and U.S. Amateur titles in the same year, joining Jack Nicklaus (1961), Phil Mickelson (1990), Tiger Woods (1996), and Ryan Moore (2004).
The Barclays: Held a one-stroke lead over Patrick Reed after 54 holes at The Barclays in the FedExCup Playoffs, before a double bogey-birdie-bogey finish on Nos. 16-18 resulted in a T7 at 6-under 278 with Jason Kokrak and Ryan Moore. Fowler went bogey free at Bethpage Black from the 10th hole in round one until the 11th hole in the final round, a span of 55 holes. His 55-consecutive holes without a bogey became a personal best on the PGA TOUR, besting 53 from the 2010 Memorial Tournament. This streak also marked the longest recorded in Barclays history since hole information began in 1983. Ian Poulter had the longest with 45 in 2010. The finish marked his third top-10 showing in his last four starts in the event (T9/2013, T9/2014).