Thomson was born in 1969 in Salford, Lancashire, England to Mary McAleer, who gave him up for adoption six weeks later. He was adopted from the Catholic Children's Rescue Society by Andrew and Marita Thomson, a businessman and a bookseller from Didsbury. He has one younger brother, Ben (born to his adoptive parents). He attended All Hallows Catholic High School near Preston, leaving with three O-levels. He then attended Runshaw College between 1985 and 1987, studying for four A-levels, including theatre studies. He was described as "clearly [having] a talent for comedy".
Following this, he turned down a scholarship in America to study drama at Manchester Polytechnic (now Manchester Metropolitan University).
While at university, Thomson met Steve Coogan, who secured him a job on Spitting Image. They would continue to collaborate on such programmes as Coogan's Run , the Paul and Pauline Calf video diaries (where he played 'Fat Bob') and Knowing Me, Knowing You... with Alan Partridge, which he also contributed to writing. He also appeared in Coogan's live shows as compere Bernard Righton and the two would be reunited in the 2002 film 24 Hour Party People. The two won the Perrier Comedy Award in 1992 for their act at the Edinburgh Fringe.
In 1994 Thomson appeared in the BBC sketch series The Fast Show, remaining with it until it ended in 2001. Thomson played memorable characters such as Chip Cobb, the deaf stuntman, and Roger the Nouveau football fan but it is "Jazz Club" host Louis Balfour that he is most remembered for, with the catchphrase, "Nice!" He also appeared in The Fast Show Live and the spin-off Ted & Ralph.
In 1996 he appeared opposite Maureen Lipman as Bob Acres in The Rivals at the Royal Exchange, Manchester.
He made guest appearances on various series such as Soldier Soldier and Men Behaving Badly in the 1990s before being cast as Pete Gifford in the ITV comedy drama Cold Feet. Thomson was known to the producers, who had previously cast him in a one-off drama called The Perfect Match. A series was commissioned that ran until 2003 and earned him a nomination for Best TV Comedy Actor at the British Comedy Awards 2001.
After Cold Feet wrapped, Thomson appeared in the Royal Exchange's production of Hobson's Choice (helped by his acclaimed performance in The Rivals). The Independent described his performance as Willie as "an extremely well-judged performance. With the slightest physical gesture and merest facial expression he conveys disbelief, reluctance, panic, and finally acceptance of his fate at the hands of manipulative Maggie". His performance led to a Manchester Evening News Award nomination for Best Actor in a Leading Role.
That same year he participated in the BBC series Comic Relief does Fame Academy, being was the fourth "student" to be "expelled". and in 2004, he appeared in the musical drama Blackpool as Tony Corlette.
He has also lent his voice to the revived BBC children's series Bill and Ben and Mr Windfall in Wallace & Gromit in The Curse of the Were-Rabbit. Another television series, New Street Law, about a Manchester chambers, started in 2006. Thomson plays "lovable rogue" barrister Charlie Darling alongside co-star John Hannah. The second series began in January 2007.
In February 2007 he played Sir Alan Prentice, in Kombat Opera Presents... The Applicants, a spoof opera of the BBC series The Apprentice. The programme attracted 700,000 viewers according to unofficial overnights. In March 2007 he appeared as hypnotherapist Ray Bould in the three-part ITV thriller, Mobile. The producers had Thomson lined up for the role of DI Fleming, but he wanted to read for Bould because he "was up against a friend for the same part". Later that year he filmed a guest appearance as Nigel Pearson in a second series episode of Kingdom. He returned as a full-time cast member for the third series.
In October 2008, Thomson filmed a three-episode guest stint on the ITV soap opera Coronation Street, playing electrician-cum-children's entertainer Jesse, the episodes aired in December. In January 2009, it was announced that he would reprise the role for six months. Jesse returned to Coronation Street in June, beginning a relationship with Eileen Grimshaw (Sue Cleaver). He is expected to leave in 2010, after his contract was not renewed.
He is also the narrator on the ITV2 programme Ghosthunting With... narrating with Yvette Fielding.
In 2010, Thomson played the part of Harry Kershaw in the Coronation Street spin-off, The Road to Coronation Street.
In January 2008 he played Mike (Topaz) in BBC Radio 4's comedy drama series 'Pick Ups'. BBC Radio 4 - Pick Ups
On 12 April 2008, Thomson began hosting the Saturday lunchtime slot on BBC Radio Manchester. His stint ended on 22 November 2008.