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.
At the PGA Championship, Fowler carded 74-69-75-68 to finish with a six-over par total of 286, in a tie for 51st place. Early on the third day Fowler rocketed up the leaderboard with three birdies in the first five holes only to falter later in the round with two triple bogeys, effectively ending his hopes of a first major championship and PGA Tour win.
Lowry won for the first time as a professional in 2012, at the Portugal Masters in October. He shot a 67 to tie for the lead with the Englishman Ross Fisher, who made bogey on the final hole after missing a four-foot putt. The victory lifted Lowry back into the Official World Golf Ranking top 100 and made him eligible to compete in the WGC-HSBC Champions.
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.
On 23 November 2011, Lowry was again loaned out to play in the Championship, this time to Millwall until 3 January 2012. He followed Aston Villa team-mate Nathan Baker who also signed on loan for Millwall two days earlier. Lowry made his Millwall debut three days later, where he played 90 minutes, in a 0–0 draw against Crystal Palace. His impressive display at Millwall soon earned a loan extension. Weeks later on 13 January 2012, Lowry was sent-off in the 22nd minutes after stamping on Nikola Žigić, which saw Millwall lose 6–0. Three years on after signing for Birmingham City, Lowry stated, quoting: "Whatever club I play for I fully commit to that club at the time. I play with my heart on my sleeve. Sometimes in the past I have gone overboard but I was a younger player then, I have learned a lot from these types of experiences. But I am an aggressive player, that’s the way I like to play and I can’t change the way I play. I will use my experience now and be a bit more clever."'