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.
Quicken Loans National: Starting the final round of the Quicken Loans National seven shots back, the Quicken Loans ambassador recorded a career-best nine birdies to post his low round of the week, a 5-under 65 to finish T3. Marked his third top-five in his last four starts. Chances for victory took a serious hit with a double bogey (the only one of the final round) on No. 14, the easiest hole in the final round. Marked second top-three finish in six starts at the Quicken Loans National (2015-2nd).
In the 2013–14 season, Lowry suffered a minor thigh strain in the club's pre-season friendly. Despite this, Lowry remained in the first team under the new management of Steve Lomas until he received a straight red card after a foul on Will Hughes, in a 5–1 loss against Derby County on 14 September 2013. After serving a three match ban, Lowry remained on the bench without playing for four matches Lowry made his first team return on 2 November 2013 when he came on as a substitute for Scott Malone against Burnley. However, his return, after spending two months without playing, was a disastrous when he scored an own goal, which saw Millwall drew 2–2. After this, Lowry was out of the first team, demoted to the substitute bench between mid-November and mid-December until he made his return on 26 December 2013, in a 4–0 loss against Watford. On 28 January 2014, Lowry was sent-off for the second time this season in the late-minutes against Sheffield Wednesday after fighting with Giles Coke, who also was sent-off as well, with both side drew 1–1. After serving a four match ban, Lowry was in the first team throughout February and March until he suffered a foot injury that kept him out for the remainder of the season. Lowry went on to finish the 2013–14 season, making twenty-two appearance.
BMW Championship: Entered the BMW Championship No. 36 in the FedExCup standings, with his T39 finish at Conway Farms outside Chicago leading to a final ranking of No. 38. Advanced to the TOUR Championship by Coca-Cola in 2012 (finished No. 28 in the FedExCup), but other three seasons led to near misses of cracking the top 30 in the FedExCup (No. 43 in 2011 and No. 32 in 2010).
THE PLAYERS Championship: A week after collecting his first PGA TOUR victory, nearly became the first player since David Duval (1997) to post first two TOUR victories in back-to-back weeks, finishing T2 at THE PLAYERS, two strokes behind winner Matt Kuchar. Holed a birdie attempt from 21 feet, 7 inches on the par 3 17th in the final round to move to 11-under but couldn't convert a 7-foot, 7-inch birdie on No. 18 that would have given him the clubhouse lead at 12-under. Recorded his fifth career runner-up finish on TOUR in his 73rd start. His T2 performance came in his third start at THE PLAYERS and first in which he made the 36-hole cut. Moved into contention with a 66 in the third round, a career low at TPC Sawgrass. Entered the final round three shots off the 54-hole pace.
Enjoyed a stellar rookie season, with seven top-10 finishes and a 32nd-place finish in the FedExCup standings that led to him winning PGA TOUR Rookie of the Year honors. Finished inside the top 30 on the money list to qualify for the Masters and the U.S. Open. Played in first three Playoff events, slipping from 21st to 32nd and out of the TOUR Championship.
U.S. Open: Playing alongside eventual-champion Martin Kaymer in the final pairing Sunday, followed up his career-best round (3-under 67) in a U.S. Open with a final-round, 2-over 72 to remain T2 (the sixth runner-up finish of his career). It was his best performance in six U.S. Open starts (previous-best finish was a T10 in 2013). It was also his top major championship showing among his 18 starts (previous-best finishes were T5s at the 2011 Open Championship and the 2014 Masters). His pairing with the 29-year-old Kaymer was just the third final grouping at the U.S. Open since 1965 with two players in their 20s. The others were John Mahaffey (28) and Jerry Pate (22) in 1976 and Woods (26) and Sergio Garcia (22) in 2002.
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.