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.
World Golf Championships-Accenture Match Play Championship: In his fourth consecutive start at the World Golf Championships-Accenture Match Play Championship, fought his way to the semifinals Sunday morning against Ernie Els. Got off to a hot start, leading for seven of the first nine holes. With a shift of momentum, Els battled back and won three consecutive holes (Nos. 10-12) to gain a 2-up lead. Following an eagle and par on Nos. 13 and 14, he squared up the match. An Els birdie-3 at No. 18 sent the match to extra holes. A birdie-3 at the 19th hole (No. 1) gave him the upset win over Els.
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.
Lowry received his first call-up to the full Australia squad for a friendly against the Netherlands in Sydney and the Asian Cup qualifier against Oman in Melbourne in October. He did not play in either match. On 11 May 2010 he was selected as part of Pim Verbeek's 30-man provisional squad for the 2010 World Cup, and travelled to South Africa, but was not included in the final 23-man World Cup squad. Lowry was named in Han Berger's 18-man squad for an August 2010 friendly against Slovenia, but he did not appear in the match.
The Honda Classic: After beginning the final round of The Honda Classic with a four-stroke lead, posted a 1-over 71 to win by the same margin for his fourth career PGA TOUR title. It marked the first of five 54-hole leads he converted to victory. Opened with back-to-back 66s for the second consecutive year and posted a 65 in the third round to post the best 54-hole total since the event moved to PGA National in 2007 at 13-under 197. Seized the 54-hole lead with the widest margin of his career entering a final round. Turned in 2-over 37, but posted three birdies on the back nine to take command of the tournament. Despite bogeys on the 71st and 72nd holes, claimed his first victory since the 2015 Dell Technologies Championship. Finished the week second in Strokes Gained: Putting (7.392) and moved to 10th in the FedExCup standings and ninth in the Official World Golf Ranking, his first time in the top 10 since the 2016 BMW Championship.
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.