From 1964 to 1969 he attended Alsop High School in Walton, and was expelled halfway through sixth form. After that, Sayle took a foundation course in art at Southport, before attending Chelsea College of Art and Design in London. He attended Garnett College, Roehampton, a training college for teachers in further education.

Around the age of 15, Sayle decided to join the Young Communist League, but only went to a few meetings. ‘The Soviet Union was going soft and…China with the Cultural Revolution was really the way to go…’. In 1968, he joined a Maoist organisation. In 2009, he said that, while no longer active in left politics, “I still would adhere to those philosophical and economic ideas of Marxism that I got when I was sixteen. … it’s seemed to me as true now as it did then”.

In 1974, Sayle married Linda Rawsthorn. He lives in Bloomsbury in central London and is a keen cyclist. He also owns a house near Granada, in southern Spain.

When the Comedy Store opened in London in 1979, Sayle responded to an advert in Private Eye for would-be comedians and became its first master of ceremonies. In 1980, comedy producer Martin Lewis saw Sayle perform at the Edinburgh Festival Fringe and became his manager.

Sayle’s early work included several performances for Capital London. In 1979 he wrote and performed the radio series, Alexei Sayle and the Fish People, for which he won a Pye Radio Award (later known as the Sony Radio Awards). Sayle later released an album based on the show, The Fish People Tapes. This was followed by Alexei Sayle and the Dutch Lieutenant’s Trousers in 1980, the name being a reference to John Fowles’ book. He has since contributed to many other radio shows, including writing the five-part sitcom series, Sorry About Last Night (1999), in which he also played the leading role. On 3 November 2006 he presented Chopwell Soviet, a 30-minute programme on BBC Radio 4 that reviewed the Chopwell miners 80 years after the village of Chopwell became known as Little Moscow. Sayle returned to Radio 4 in 2016 with Alexei Sayle’s Imaginary Sandwich Bar. In 2019, he narrated the dramatisation of four of his short stories in the series Alexei Sayle’s The Absence of Normal, again on Radio 4.

Sayle has released five comedy singles with full musical backing and one live recording from the Comedy Store in London 1981. This was a double A side with Alex Arundel the London based Scottish songwriter and founding member of Alternative Cabaret with the song “When The Gold Runs Dry”, being the other A side. His most successful single was “‘Ullo John! Gotta New Motor?” which achieved Top 20 chart success in the UK upon re-release in 1984. Produced by Clive Langer and Alan Winstanley (who also produced for Madness and Elvis Costello), the record in its 12-inch version achieved notoriety owing to its extensive use of profane language. The two follow up singles, “Didn’t You Kill My Brother?”, and “Meanwhile”, were taken from the album Panic, the cover of which parodies the cover of the Michael Jackson album Off the Wall.

Sayle’s first high-profile television appearances were on Central Independent Television’s late-night alternative cabaret show O.T.T. (1982). He left nine weeks into the show’s run to tour Australia with the Comic Strip. He played various roles in the situation comedy The Young Ones (1982–1984), along with Adrian Edmondson, Rik Mayall, Nigel Planer and Christopher Ryan. In the programme Sayle portrayed several members of an Eastern European family; the Balowskis. In 1985, he appeared in the Doctor Who serial Revelation of the Daleks. In a column for a British tabloid newspaper around the same time, he indicated that he wanted to become the “first Socialist Doctor.” He also appeared in several episodes of The Comic Strip Presents… between 1985 and 1993, most notably playing the two leading roles in “Didn’t You Kill My Brother?” which he co-wrote with David Stafford and Pauline Melville. Sayle has co-written and starred in many other programmes, including three series of Alexei Sayle’s Stuff (1988–1991), two series of The All New Alexei Sayle Show (1994–1995) and one series of Alexei Sayle’s Merry-Go-Round (1998).

In 1988, Sayle played the role of Trinculo in Shakespeare’s The Tempest, directed by Jonathan Miller at the Old Vic theatre in London. Sixteen years on from his last stand-up comedy tour, Sayle returned in 2011 as an MC, compering the middle section of At Last! The 1981 Show, curated by Stewart Lee at the Royal Festival Hall. Although this was mainly a nostalgia night with comedians such as Nigel Planer and Norman Lovett revisiting their material from the 1980s, Sayle premiered some new material that was more anecdotal than his previous work. Sayle says of his old style: “What I was doing, which I hadn’t realised, was a comic persona. The guy in the tight suit was actually a creation. I thought it was me in a sense but it wasn’t.”

In 1989, Sayle was awarded an International Emmy for Stuff. In conversation with Mark Thomas on BBC Radio 4’s informal chat-show Chain Reaction, Sayle revealed that the first he knew of the award was when he watched Channel 4 News and saw, to his amazement, Benny Hill collecting the award on his behalf. In 1990, Sayle had a fatwa proclaimed against him by a Muslim cleric from Syria after a joke on his BBC comedy show Stuff. This fatwa has never been withdrawn.

Sayle was signed in 1992 to a seven-year contract to play an Eastern European chef as a regular character on the American sitcom The Golden Palace, the sequel to The Golden Girls, but was fired and replaced by Cheech Marin before the pilot was shot. The series was cancelled after one season.

Sayle alternates his comedy work with performances as a character actor ranging from serious (Gorky Park, 1983) to humorous (Indiana Jones and the Last Crusade, 1989). He appeared in the 1992 Carry On film, Carry On Columbus along with various modern comedians including Comic Strip founder Peter Richardson, as well as members of the original Carry On team.

In 1994 he presented the miniseries Drive, which gave advice for safe driving through Sayle’s signature form of humour interspersed with serious pieces. In 2008, he wrote and presented Alexei Sayle’s Liverpool, a three-part television series in which he reconnected with his home town. He stated in the programmes that on first hearing that Liverpool was to be awarded the European Capital of Culture, he received much criticism for describing the city as “philistine”. He now feels that he does not know whether or not his original statement was true, but as a result of making the series he does now consider Liverpool to be his home, and he has vowed to go back there more often in the future.

Sayle has written two short story collections, five novels, including a graphic novel and a radio series spin-off book, as well as columns for various publications. His book Great Bus Journeys of the World, co-written with David Stafford, is mostly a collection of his columns for Time Out and the Sunday Mirror. He was one of eight contributory authors to the BBC Three competition End of Story, in which members of the public completed the second half of stories written by established authors. The winning entry to Sayle’s story, Imitating Katherine Walker, was written by freelance writer Arthur Allan. Sayle’s autobiography Stalin Ate My Homework, which deals with his early life and which he describes as a ‘satirical memoir’, was published in 2010. In 2012 he joined The Daily Telegraph as a motoring columnist. In early 2015 he toured giving readings from the second volume of his autobiography Thatcher Stole My Trousers, published in 2016.

Alongside artists such as Isy Suttie and Jim Bob, Sayle appeared at the fourth “Nine Lessons and Carols for Godless People” event at the Bloomsbury Theatre in December 2011. In January and February 2012, he compered four nights of stand-up comedy at the Soho Theatre. He completed a full UK stand-up tour in October and November 2012, and a sixteen-night residency at the Soho Theatre in January and February 2013, where he performed new material. He played a further ten nights at the Soho Theatre in April 2013. He also performed at the 2013 Edinburgh Festival Fringe. He has toured extensively in recent years.

Sayle replaced Rolf Harris as the narrator for the Nick Junior and Milkshake! series Olive The Ostrich. Episodes featuring Sayle’s narration commenced broadcasting on 22 July 2013.

Sayle is a critic of fox hunting and was among more than 20 high-profile people who signed a letter to Members of Parliament in 2015 to oppose Conservative Prime Minister David Cameron’s plan to amend the Hunting Act 2004.

In February 2016, Sayle said of Labour Party leader Jeremy Corbyn: “He’s ascetic and morally incorruptible. The propaganda that’s thrown against him is disgraceful. Until he appeared, you had to vote for one kind of Oxbridge twat or another, people who all go to the same dinner parties, people like the Ed Ballses and George Osbornes. Jeremy has shown that, within a democratic tradition, other things are possible.” In 2016, he wrote a comment piece for The Guardian saying that he was happy to mock New Labour in his act but now that Corbyn was about to “reform the party in his own image – ascetic, socialist, kindly and ethical” he would stop making jokes about Labour.

In May 2018, regarding the expulsion of Marc Wadsworth from the Labour Party, Sayle commented: “The Party should walk over broken glass to beg people of Marc’s calibre to work with them – they are very few and Marc is one of the best. There is a battle going on to destroy and reverse the unexpected and amazing gains the left has made in the last three years. Marc is a casualty in that battle and I am joining the fight to see him re-instated to the front line.”

In November 2019, along with other public figures, Sayle signed a letter supporting Labour Party leader Jeremy Corbyn describing him as “a beacon of hope in the struggle against emergent far-right nationalism, xenophobia and racism in much of the democratic world” and endorsed him in the 2019 UK general election. In December 2019, along with 42 other leading cultural figures, he signed a letter endorsing the Labour Party under Corbyn’s leadership in the 2019 general election. The letter stated that “Labour’s election manifesto under Jeremy Corbyn’s leadership offers a transformative plan that prioritises the needs of people and the planet over private profit and the vested interests of a few.”

In January 2020, he was condemned by some Jewish groups after being one of thousands to sign an open letter criticising Rebecca Long-Bailey and other Labour leadership candidates for saying they would sign a ten point pledge by the Board of Deputies of British Jews intended to combat anti-semitism should they be elected. Opponents have stated that the pledges are political interference by an organisation overtly hostile to today’s Labour Party and everything it stands for. The letter was organised by Momentum activist, Jackie Walker and former Labour MP Chris Williamson, both of whom were expelled from Labour in relation to charges of anti-semitism.