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.
Waste Management Phoenix Open: Two weeks after the win in Abu Dhabi, made his eighth consecutive start in the Waste Management Phoenix Open, where he found himself three strokes off the lead after 54 holes. A final-round 4-under 67, capped off by a clutch birdie on the 72nd hole, forced sudden death with Hideki Matsuyama. On the fourth extra hole, the par-4 17th, an errant tee shot found the water hazard for the second time of the day. Matsuyama made par to win. Ranked second in Strokes Gained: Tee To Green and T1 in Strokes Gained: Total at TPC Scottsdale.
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.
After Lowry's loan spell at Leeds was coming to an end, on 11 May he signed a new two-year contract extension at Aston Villa. It was a remarkable few days for Lowry, he was promoted with Leeds, received a call up to Australia's World Cup Squad and on the same day he signed a new two-year deal with Villa. Despite signing a contract with the club, Leeds United was considering re-signing him for the second time ahead of the 2010–11 season, but never happened.
BMW Championship: After entering the final round of the BMW Championship in a second-place tie with Jason Day (five strokes behind Marc Leishman), recorded a 4-under 67 to finish T2, his 11th career runner-up on the PGA TOUR. Week was highlighted by a career-best, six consecutive birdies in the first round on Nos. 12-17. Chipped in from 64 feet on the 17th.
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.