In 2000 Chris Addison co-hosted the short-lived Channel 4 comedy series Dotcomedy with Gail Porter. This was a late-night, risque show featuring video clips and other humour derived from the internet.

From 2003 to 2005 Addison wrote a fortnightly Finance column for The Guardian titled "Funny Money". On alternate weeks, when the column was not written by Addison, writing duties passed to fellow stand-up Dominic Holland.

First broadcast in 2004, Addison co-wrote and co-starred in the political satire The Department, along with John Oliver and Andy Zaltzman. It ran for 14 episodes over three series on BBC Radio 4, ending in 2006.

Since 2005, Addison has appeared in the BBC television satirical comedy series The Thick of It as Oliver "Ollie" Reeder, Junior Advisor (later Special Advisor) to the Secretary of State (Department of Social Affairs and Citizenship). He appeared in all episodes of the first three series, as well as the two specials 'Rise of the Nutters' and 'Spinners and Losers'. Chris Addison reprised his role as Ollie when The Thick of It returned for a fourth series.

Addison has written two books, both published by Hodder and Stoughton: Cautionary Tales for Grown Ups in 2006 and It Wasn't Me: Why Everybody is to Blame and You're Not in 2008.

In July 2008, BBC Two aired Lab Rats, a sitcom starring Addison and co-written with Carl Cooper. Lab Rats featured cast members Jo Enright, Geoffrey McGivern and Dan Tetsell, with whom Addison had worked previously on the radio adaptations of his one-man shows The Ape That Got Lucky and Civilisation.

Addison appeared on The Graham Norton Show on 16 April 2009 promoting In the Loop. On 18 April 2010 he appeared on The Andrew Marr Show to comment on the week's political issues, including the volcanic ash cloud from Iceland and The First Election Debate.

He appeared on Skins as Professor David Blood, the college Director of Roundview College and father of third Generation character Grace Violet. On 4 November 2010 Addison hosted the BBC's Have I Got News For You, having previously been a guest on the show.

In 2011 he took part in three shows of the 16-date Uncaged Monkeys tour along with Brian Cox, Robin Ince, Ben Goldacre, Simon Singh and Dara Ó Briain.

In July 2013 he received an honorary degree from the University of Birmingham.

In 2014 Addison starred in the Sky Living series Trying Again.

In February 2016 Addison took the speaking role of Smith, an Englishman, in the French opera L'Étoile at The Royal Opera House, London.