Lowry was the 2007 Irish Amateur Close Champion, defeating Niall Turner 4 & 3 in the final. While still an amateur in May 2009, he won The Irish Open on the European Tour, defeating Robert Rock on the third hole of a sudden death playoff. The win, on his tour début, made him just the third amateur to win on the European Tour, following Danny Lee earlier in the 2009 season, and Pablo Martín in 2007. Lowry shot a 62 to equal the lowest ever by an amateur on the circuit and led from the second round onwards.
At the 2016 U.S. Open at Oakmont Country Club near Pittsburgh, Lowry shot 65 (−5) in the third round for 203 (−7) and a four-stroke advantage over Dustin Johnson and Andrew Landry at the 54-hole stage. The 65 was Lowry's joint career best round at a major championship. Due to weather delays on Thursday, the third round was not completed until early on Sunday, and Lowry birdied two of his remaining four holes to extend his two stroke overnight lead to four. In the final round he was in contention for the title, within one shot of Dustin Johnson after 12 holes, before three consecutive bogeys on holes 14, 15 and 16 ended his chances. He finished the tournament tied for second place, with a final round score of 76.
After a tie for fifth at the Masters in April, Fowler had his best finish of 2014 at the U.S. Open at Pinehurst No. 2 in North Carolina. Fowler was runner-up with Erik Compton at −1, best finishes for both at a major, but they were eight strokes behind champion Martin Kaymer. Fowler had another second-place finish, at the Open Championship at Royal Liverpool Golf Club in Hoylake, England. He began the final round six strokes behind Rory McIlroy and finished the day tied for second with Sergio García at −15, two strokes behind McIlroy. At the next major in August, the PGA Championship, Fowler, Phil Mickelson, Henrik Stenson, and McIlroy battled for the title on a rain-soaked Valhalla Golf Club, near Louisville. Despite holding the lead for a good portion of the day, Fowler tied for third. He was only the third player, along with Jack Nicklaus and Tiger Woods, to have finished in the top 5 in all four majors in one calendar year, but the first not to win (Jordan Spieth became the fourth player in 2015). Fowler had 10 top-10 finishes during the 2013–14 season. His 8th-place finish at The Tour Championship moved him to 10th in the world golf rankings.
Kolon Korea Open: Won his first tournament as a professional, the Kolon Korea Open on the OneAsia Tour, when he rolled to a six-stroke win over Rory McIlroy at Woo Jeong Hills CC in early October. He took control of the tournament in the third round when he shot an 8-under 63. He followed that with a 3-under 68 Sunday. The victory was worth a little under $250,000.
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.
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."'
At the first FedEx Cup playoff event, Fowler finished T52 at The Barclays in the last week in August. The following week he again finished T52 at the Deutsche Bank Championship, the second FedEx Cup playoff event, after carding a disappointing six-over par final round 77. At that point Fowler was positioned 37 in the FedEx Cup points standings and required a strong performance at the BMW Championship to qualify in the top thirty for The Tour Championship; a performance which eluded him, finishing in 48th place. In finishing 43rd in the FedEx Cup, Fowler earned a $132,000 bonus.
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).