He made 11 appearances in the Premier League for Sunderland in the 2002–03 season and has made over 200 appearances in the Football League, mostly for Sunderland, Doncaster Rovers and Leyton Orient.
Thornton began his career with Football League Second Division club Tranmere Rovers in 2001, for whom he made 13 appearances in the 2001–02 season, scoring once against Wigan Athletic. He was out of contract in summer 2002 and joined Premier League side Sunderland in July 2002, for a fee of £225,000 agreed at tribunal, amid allegations by Tranmere that Sunderland had breached FA and Football League regulations by making an illegal approach for Thornton, for which Sunderland were later fined £1,500.
Thornton did not feature in the Sunderland first team at the beginning of the 2002–03 season and joined Blackpool on a one-month loan in November 2002. He made his debut for Sunderland in a FA Cup third-round replay win over Bolton Wanderers in January 2003, impressing manager Howard Wilkinson who said, "That was the first full game I've seen Sean in and I must say it was a very promising and mature performance. He's certainly a player we want to keep an eye on and bring on but it's now up to him to show he can produce that standard consistently." He made 14 appearances for Sunderland in the 2002–03 season, despite missing part of the season after being called up for the Ireland Under-20 squad for the World Youth Championships in the United Arab Emirates in March 2003. In April 2003, he scored with an impressive volley to give Sunderland an early lead against Chelsea although Sunderland went on to lose the match. He was unable to help Sunderland from being relegated at the end of the season. All 11 of his Premier League appearances that season ended in defeat, giving him the record for worst season that was broken 13 years later by Aston Villa's Jack Grealish.
Thornton made 13 appearances for Sunderland at the start of the 2003–04 season, before suffering an ankle injury in a reserve team game in October 2003. He returned to the side in January 2004 and made a further 17 appearances, helping Sunderland to the semifinal of the FA Cup, and the Division One playoff semifinal. Thornton was unable to command a regular first team place at the start of the 2004–05 season and by September 2004, was seeking a move away from the club. A transfer did not materialise and with his first team chances limited, he made only 20 appearances for Sunderland in the 2004–05 season. At the end of the season, he was transfer listed.
Following Sunderland's promotion to the Premier League in May 2005, Thornton was sold to Football League One club Doncaster Rovers in July 2005 for a club record fee of £175,000. He made 36 appearances for Doncaster in the 2005–06 season, missing several weeks owing to an ankle injury suffered in September 2005 that needed surgery. He helped Doncaster reach the quarterfinals of the Football League Cup, putting in a fine performance and scoring the third goal when Doncaster beat Premier League club, Aston Villa 3–0 in November 2005. Manager Dave Penney praised Thornton, saying: "It was a great goal for Sean and he's looking much brighter and sharper these days, and long may that continue." After the game, Thornton said that he felt had made the right move in the summer, saying "It was a gamble for me. I still had two years left on my contract at Sunderland. It was one of them – would I go, would I not go? Obviously we're playing good football and I think I made the right decision. Now, hopefully, we can carry on the success until the end of the season and get promoted. That's the main thing." In the 2006–07 season, Thornton made 41 appearances, and helped Doncaster to victory over Bristol Rovers in the Football League Trophy final in April 2007 when he swung in a corner kick for Graeme Lee to head in to score the extra time winner at the Millennium Stadium, Cardiff.
Thornton was released by Doncaster manager, Sean O'Driscoll at the end of the 2006–07 season, and joined another League One side, Leyton Orient in July 2007 on a two-year contract. Orient manager Martin Ling said that he was "... pleased to have Sean on board. We've been looking for a creative midfielder and Sean fits the bill perfectly. He will fit into our style of play and I believe we have signed a quality player." He scored on his debut against Southend United in August 2007, with a spectacular free kick from 30 yards in a 2–1 away win, and went on to make 34 appearances in the 2007–08 season, although he missed four matches after being sent off in October 2007 for allegedly punching another player. The following season, he joined Shrewsbury Town in September 2008 on a one-month loan, where he scored once against Darlington. On his return to Orient, he regained his place in the first team under new manager Geraint Williams and made a total of 34 appearances for Orient in the 2008–09 season in addition to his loan spell at Shrewsbury Town. He signed a new one-year contract with Orient in June 2009, with the option of a further year, but was released by Williams' replacement Russell Slade on 9 May 2010 after putting on too much weight.
Sean Thornton became something of a cult hero at Orient, leading to local folk-punk hero Steve White recording and releasing a song in praise of Thornton.
After false reports that he had signed for FC Metalist Kharkiv, Thornton signed for Aberystwyth Town on a short term contract on 13 September 2011, in a move that was described by the club as 'arguably the biggest signing in Welsh Premier League history'. The midfielder scored his first goal in Aber colours on 11 November 2011, as the Seasiders hammered Port Talbot Town 4-0 at the Genquip Stadium. On 16 November 2011, it was announced that Thornton had agreed to extend his stay with Aberystwyth Town until the end of the 2011/12 Welsh Premier League campaign. He scored his second goal for the club in the 1-1 draw with Afan Lido. He is signed for another season (2012–13) at Aberystwyth Town
After doing pre season with Chris Herbert's men Thornton signed for the ambitious North Wales club on a years pay as you play deal, while he proves his fitness from a ruptured Achilles' tendon. Thornton was influential in Conwy Boroughs undefeated start to the season, also scoring twice in 3 games. But after 6 games in to the 2013/14 season Sean Thornton was released from Conwy for breaching Club rules.
On 3 January 2014, Thornton agreed to join Welsh Premier League side Bala Town. He was handed the number nine shirt.
On 4 January 2015 Sean agreed to sign for hometown club Drogheda United in what would be his first experience of playing in the League of Ireland. Thornton signed along with former Athlone Town player Sean Brennan. Thornton made his debut against Bray Wanderers in a 1-0 away win. In his next game Thornton set up the winner with a free kick in a 3-2 win against Sligo Rovers.
On November 26 Thornton resigned with the club on a year deal. He said "I am looking forward and determined to get the club back into the top tier where it belongs."
Thornton represented the Republic of Ireland Under-16 team at the 2000 UEFA European Under-16 Football Championship and the Under-19 team at the 2002 UEFA European Under-19 Football Championship.
(to end of 2008–09 season)Sunderland
Football League Championship Champions: 2004–05
Thornton's younger brother, Kevin, is also a professional footballer.