With 14 winners' medals, he is one of the most decorated Irish footballers of all time; only Denis Irwin, Roy Keane, Steve Heighway and Ronnie Whelan have accrued more honours.

He spent loan spells at AFC Bournemouth and Royal Antwerp before establishing himself in the Manchester United first team, going on to make 393 appearances and scoring 15 times in all competitions across 12 seasons.

[8][9] After a loan to Belgian side Royal Antwerp, he returned to Manchester and began to feature in the United first team in the 2002–03 season, demonstrating versatility by playing at left-back, right-back, centre-back and central midfield during the successful 2002–03 Premier League campaign.

[10] He was criticised for his lacklustre performances that season, and was reportedly one of the players lambasted by United veteran Roy Keane in a controversial interview on the club's MUTV channel.

[17] O'Shea then started the 2009 Football League Cup final, before being replaced by Nemanja Vidić on 76 minutes, United won the game 4–1 on penalties.

[19] O'Shea started and played the full 90 minutes in the 2009 Champions League final 2–0 loss to Barcelona, and by many accounts was one of United's better performers on the night.

[25] He captained the team for the third time in the second leg of United's 2010–11 UEFA Champions League semi-final victory over Schalke 04,[26] but was not named in the squad for the final.

[29] In his first appearance for Sunderland, a friendly against Arminia Bielefeld, O'Shea picked up a hamstring injury, ruling him out for the rest of pre-season and the start of the 2011–12 campaign.

[32] O'Shea scored his first club goal for more than four years to help Sunderland clinch a 4–1 away win over Derby County to move off the bottom of the Championship table on 30 March 2018.

[35][36] O'Shea made his Reading debut on 14 August 2018, coming on as an 82nd-minute substitute for Yakou Méïté in a 2–0 home win against Birmingham City in the EFL Cup.

[37] He made his league debut for the club on 22 September in a 3–0 home victory over Hull City in a match which he received a straight red card for a foul on Chris Martin.

[38][39] O'Shea announced his retirement from football on 30 April 2019,[40] his 38th birthday, and made his final career appearance five days later in a goalless draw at home to Birmingham City where he received a guard of honour from both sets of players.

[41] O'Shea earned his first senior cap for the Republic of Ireland on 15 August 2001, when manager Mick McCarthy sent him on as an 84th-minute substitute for Gary Kelly in a friendly against Croatia at Lansdowne Road.

On 1 April 2009, in the game against Italy, he was elbowed in the forehead by Giampaolo Pazzini, who earned the record for the fastest sending off in Italian football history.

[44] Including the second leg of their play-off victory over Estonia, made nine appearances in UEFA Euro 2012 qualifying, as Ireland reached the continental tournament for the first time since 1988.

On 15 August 2012, his 80th cap, O'Shea captained Ireland for the first time, in a goalless friendly draw against Serbia at the Red Star Stadium in Belgrade.

[46] O'Shea was scheduled to face Spain on 11 June 2013 at Yankee Stadium in New York, but was ruled out of the game over the sudden death of his uncle Jimmy O'Leary.

[55] Over a year after his penultimate game for Ireland, O'Shea played his final of 118 matches on 2 June 2018, a 2–1 friendly win over the United States at the Aviva Stadium.

[64] When Wayne Rooney was appointed manager of EFL Championship club Birmingham City in October 2023, O'Shea joined his staff as a first-team coach.