From 2007 to 2024 he played Bryn West in the BBC sitcom Gavin & Stacey for which he received a BAFTA Award nomination for Best Comedy Performance.

He has acted in a number of shows for the BBC with Steve Coogan starting with 24 Hour Party People (2002) and A Cock and Bull Story (2005).

While at Dumbarton, he once stole the lunch money of fellow pupil Catherine Zeta-Jones (which he admitted while participating in a series 4 episode of Would I Lie To You?).

[8] In 1994 and 1995 Brydon appeared in numerous episodes of the original Radio Wales version of the cult comedy Satellite City with Boyd Clack.

[9][10] During an episode of Would I Lie To You?, Brydon admitted that he had pretended on the phone to be his own agent, using one of his repertoire of different voices in the early part of his career.

[13] He is also known for voice-over work in television advertising, including for Renault, Tango, The Times, Tesco, Abbey National, Sainsbury's, McDonald's, Pot Noodle, Domino's Pizza, Crunchy Nut Cornflakes, The Observer and Fairy Liquid.

[15] In 2000 he made his mark in television comedy, with two series which he co-wrote and performed for the BBC: Human Remains, co-written by Julia Davis.

Brydon plays as Keith Barret, a naïve taxi driver going through a messy divorce from his wife, Marion, who, though he fails to realise it, has had a long-standing affair with her colleague, Geoff.

In 2006 he parodied comedy panel shows such as QI, Mock the Week and Have I Got News For You in the BBC Three series Rob Brydon's Annually Retentive.

Ed Potton of The Times found that the series "provides the perfect platform for host Brydon, playing a demonic version of himself, to mimic (often hilariously) and abuse (often brutally) his guests".

Dana Stevens of Slate wrote, "Rob Brydon, plays Tristram’s Uncle Toby, a blustering war veteran with a wound in an unspeakable place.

[17] From 2007 to 2010 Brydon gained prominence for his leading role as Uncle Bryn in the BBC sitcom Gavin & Stacey starring Matthew Horne, Joanna Page, and James Corden.

[citation needed] When the team went on a tour of non-broadcast stage shows, Brydon filled in as chairman when Lyttelton was in hospital to repair an aortic aneurysm.

His character Bryn West in Gavin & Stacey, written by Ruth Jones and James Corden, allowed him to return to his South Wales roots.

In February 2009, it was announced that Brydon would be one of three people to replace Lyttelton as chairman of the 51st series of I'm Sorry I Haven't a Clue (the others being Stephen Fry and Jack Dee).

[23][24] Between September and October 2011, Brydon starred alongside Kenneth Branagh in Francis Veber's play The Painkiller at the Lyric Theatre in Belfast.

In 2010 Brydon took part in Channel 4's Comedy Gala, a benefit show in aid of Great Ormond Street Children's Hospital, filmed live at the O2 Arena in London on 30 March.

In 2015 he had a uncredited role as Master Phineus in the Kenneth Branagh directed romantic fantasy Cinderella for Walt Disney Pictures.

The following year he played Gryff in The Huntsman: Winter's War (2016) alongside Charlize Theron, Chris Hemsworth and Emily Blunt.

[32] That same year he narrated The Chasers Road Trip: Trains, Brains and Automobiles, was a contestant on Celebrity Catchphrase, and voiced The Crow in Superworm alongside Olivia Colman and Matt Smith.

In 2023 he had a brief role as Sugar Daddy Ken in Greta Gerwig's comedy Barbie starring Margot Robbie and Ryan Gosling.

In 2022 Brydon appeared in Stephen Sondheim's Old Friends revue, including alongside Haydn Gwynne in "The Little Things You Do Together", the marital battle from Company.

[37][38] On 6 October 2006, Brydon married Clare Holland, a former producer on The South Bank Show, at the church of St John the Baptist in Windsor, Berkshire.