In 2008, Fowler repeated as Sunnehanna Amateur champion. In the first round of the U.S. Open, Fowler shot a −1 (70) and was in a tie for 7th place. He was one of three amateurs to make the cut, along with Derek Fathauer and Michael Thompson. He ended the tournament tied for 60th. In October 2008 Fowler played on the Eisenhower Trophy team that finished second. He was the leading individual player.
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With this win, he entered the Official World Golf Ranking as an amateur at No. 168 and reached a career high of sixth in the World Amateur Golf Ranking. Walker Cup captain Colin Dagleish described the win as "fairytale stuff", adding: "You'd have to say that Shane's victory was the biggest (of the three amateur wins). To win your own national Open is quite something. It was unbelievable, it really was." The win was only the second home victory since 1982 and the first since Pádraig Harrington in 2007. Harrington himself was also full of praise: "It's fabulous for Irish golf. You only have to look at the fact it is such a rarity for an amateur to win, such a rarity for an Irish player to win the Irish Open. So, on a lot of fronts, it is a big deal. It was very impressive."
Lowry did not win on the European Tour from 2016 to 2018 but was joint runner-up in the 2017 DP World Tour Championship, Dubai and runner-up in the 2018 Andalucía Valderrama Masters. In January 2019 he won the Abu Dhabi HSBC Championship by a stroke from Richard Sterne. Lowry led by 3 strokes after three rounds but was two-over-par after 11 holes of his final round and dropped 4 shots behind Sterne. However he finished with 3 birdies in the final 7 holes, while Sterne had two bogeys, giving Lowry the victory.
Presidents Cup: Closed out his second consecutive Presidents Cup appearance with a 6-and-4 victory over Emiliano Grillo, helping lead the United States to a 19-11 win over the International Team. Compiled a 3-0-1 overall record, highlighted by victories the first two days with teammate Justin Thomas in Foursomes (6 and 4 over Charl Schwartzel and Hideki Matsuyama) and Four-ball (3 and 2 over Branden Grace and Louis Oosthuizen).
the Memorial Tournament presented by Nationwide: Erased a five-stroke deficit in the final round and briefly held the lead before eventually shooting a final-round 70 to finish runner-up in the Memorial Tournament, three shots behind Jason Dufner. Hit a 350-yard drive on the 72nd hole and had just 136 yards to the pin when play was called for inclement weather for the second time during the final round. When play restarted, he made a costly bogey at the last to fall into a tie for second. Ranked No. 1 in fairways hit for the week with 45 of 56. Was also 8 of 11 in sand saves to rank first for the week.
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.
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.
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.
Waste Management Phoenix Open: Claimed his second runner-up finish at the Waste Management Phoenix Open, one shot behind Hunter Mahan. Had birdie opportunities on the last three holes but unable to catch Mahan. Previously lost in a playoff to Troy Matteson just down the road at Grayhawk GC in the 2009 Frys.com Open. Had he won at TPC Scottsdale, would have become the first Sponsor Exemption to do so since Jason Gore (2005 84 Lumber Classic). Lee Westwood later won in June as a Sponsor Exemption at the St. Jude Classic presented by Smith & Nephew.
Lowry made his professional debut in the 2009–10 UEFA Europa League in an away fixture at Rapid Vienna. On 17 September 2009, Lowry signed a three-month loan deal with Football League Championship side Plymouth Argyle. Lowry made his Plymouth Argyle debut on 19 September 2009, playing 90 minutes, in a 3–1 loss against Newcastle United. He played 13 league games for Plymouth during his loan spell, where he impressed many and was recalled by Villa who required Lowry's services as cover after some injuries to defenders.
Hyundai Tournament of Champions: Finished T6 in a Monday-start-Tuesday-finish event, the season-opening, 54-hole Hyundai Tournament of Champions. The event "started" twice during the regularly scheduled first round Friday and later Sunday, but both times PGA TOUR rules staff halted play due to unplayable windy conditions and subsequently voided all scores that had taken place. As the first player off the tee, he ended up hitting three "opening" shots of the season.