Skinner has appeared in numerous TV comedies, including , The Office Christmas specials, My Family, Yonderland and Coupling. He was also a regular writer and performer on Katy Brand's Big Ass Show for ITV2. He appeared in series 2 of The Armstrong and Miller Show on the BBC in 2009, and the third series in 2010. He also played Reggie's chauffeur in the remake of Reggie Perrin. He has appeared twice in BBC1's sitcom My Family both as a policeman in series 5's "The Mummy Returns" and in series 10's "Desperately Stalking Susan". He also had a part in episode 4 of series one of Mongrels as an American reporter, and appeared as Captain Length-Width with Vic Reeves in the CBBC show The Ministry of Curious Stuff. In 2013 he appeared as a police officer in The Wrong Mans with Yonderland co-star Matthew Baynton. In 2014, he appeared in House of Fools as Bosh and Friday Night Dinner as Jeremy Phillips. In 2015, he appeared alongside Katherine Parkinson in BBC sitcom The Kennedys. Since 2017, he has appeared in comedian Tracey Ullman's BBC Onesketch comedy series, Tracey Ullman's Show and Tracey Breaks the News. In 2018 Skinner appeared in the second episode of series 9 of Not Going Out as a mad man hell bent on revenge. In 2019 Skinner had a recurring role in Channel 5 first homegrown drama "Cold Call" alongside Sally Lindsay.
Skinner appeared as Angelos Epithemiou on series 6 of Shooting Stars as a permanent member of Team B, replacing Johnny Vegas. In series 7 and 8, he replaced George Dawes as the score keeper. The character's signature tune is "Drop the Pressure " by Project Bassline. He is of Greek origin and resides in Neasden. He is on the dole. He was originally introduced by Bob Mortimer as a competition winner, as well as a burger van owner from 'somewhere in the North East', although this aspect of his character was gradually sidelined. As the character developed, Epithemiou showed an ongoing obsession with Ulrika Jonsson, and revealed that his burger van had been destroyed by his brother Agathius. He also appeared in a series of YouTube clips alongside David Earl whose character Brian Gittins employed him at his cafe, and who was increasingly envious of the fame Epithemiou was gaining on Shooting Stars. Skinner appeared on BBC Three show World Cup 2010's Most Shocking Moments with other celebrities, reviewing and making jokes about incidents in the 2010 FIFA World Cup. This was one of the first appearances on TV since performing as the character Epithemiou on Shooting Stars. In 2010 Skinner took the Epithemiou character on a UK tour titled Angelos Epithemiou & Friends Christmas Show; due to popular demand, venues introduced additional dates throughout December 2010.
He appeared four times on Soccer AM during 2011 and 2012, and was a guest panellist on the BBC music quiz show Never Mind the Buzzcocks in December 2011. In August 2011, Renton appeared as Epithemiou in BBC Radio 1's Fun & Filth Cabaret, part of the Edinburgh Festival Fringe. He ended each of the shows with a HARDtalk-style interview. In December 2011 Skinner won the Best Comedy Breakthrough Artist at The British Comedy Awards for his work as Epithemiou over the previous year. In the same month, he appeared as Epithemiou on the Christmas special of The Rob Brydon Show. In 2012, he starred in his own show, The Angelos Epithemiou Show, on Channel 4. He also appeared as John Meringue in the Reeves and Mortimer quiz show Vic & Bob's Lucky Sexy Winners. Epithemiou took part in Channel 4's Come Dine with Me on 4 January 2013. He served tinned mushroom soup with white sliced bread for the starter and employing a burger van to cook his main dish. The only dish he cooked was a swiss roll for dessert: however his guests were told to go home halfway through their desserts and had to finish their food in their taxis on the way home. Epithemiou appeared alongside Debbie McGee on Pointless Celebrities in December 2018, raising money for motor neurone disease. On 1 December 2019, Epithemiou appeared on Channel 4's Sunday Brunch but only for the start of the show when guests are introduced followed by the first cooking item which he interrupted part-way through by walking into shot to announce that he was leaving.
Skinner can be seen in Tim Plester's 2006 short film World of Wrestling as a fictionalised version of wrestler Dave 'Fit' Finlay. In June 2014, it was announced that Skinner would play Simmons in Ben Wheatley's upcoming film High-Rise. Skinner appeared in Swallows and Amazons alongside Andrew Scott and Rafe Spall as a Russian Agent. He also appears in the 2016 documentary Notes on Blindness as the subject, John M. Hull, in recreations.