Briers met Ann Davies while both were at Liverpool Rep. Davies was employed as a stage manager, and had acted on television and in films from the mid-1950s. Soon after meeting, he borrowed £5 from his mother, bought an engagement ring and they were married within six months. They had two daughters, one of whom, Lucy, is also an actress; Kate (or Katie) has worked in stage management, and is a primary school Teacher.

When he left the RAF he studied at RADA, which he attended from 1954 to 1956. Placed in a class with both Peter O'Toole and Albert Finney, Briers later credited academy Director John Fernald with nurturing his talent. Graduating from RADA with a Silver Medal, he won a scholarship with the Liverpool Repertory Company, and after 15 months moved to the Belgrade Theatre in Coventry for 6 months. He made his West End debut in the Duke of York's Theatre 1959 production of Gilt And Gingerbread by Lionel Hale.

Briers made his film debut in 1960 British feature film Bottoms Up. He then took parts in Murder She Said (1961), The Girl on the Boat (1962), A Matter of WHO (1962), The V.I.P.s (1963); and Raquel Welch's spy spoof Fathom (1967).

(Television) His other early appearances included The Seven Faces of Jim (1961) with Jimmy Edwards, Dixon of Dock Green (1962), a production of Noël Coward's Hay Fever (1968) and the storyteller in several episodes of Jackanory (1969). In 1970, he starred in the Ben Travers Farce "Rookery Nook", shown on the BBC. In the 1980s he played several Shakespearean roles, including Twelfth Night. Briers was featured twice on the Thames Television show This Is Your Life in May 1972 and March 1994.

Briers spent much of his career in the theatre, including appearances in plays by Shakespeare and George Bernard Shaw. In 1967, one of his earliest successes was playing alongside Michael Hordern and Celia Johnson in the London production of Alan Ayckbourn's Relatively Speaking.

His work in radio included playing Dr. Simon Sparrow in BBC Radio 4's adaptions of Richard Gordon's Doctor in the House and Doctor At Large (1968), and a retired thespian in a series of six plays with Stanley Baxter Two Pipe Problems (2008), and later the play Not Talking, commissioned for BBC Radio 3 by Mike Bartlett. In 1986 he narrated Radio 4's "Oh, yes it is!", a history of pantomime written by Gerald Frow. Between 1973 and 1981, Briers played Bertie Wooster in several adaptations of the P. G. Wodehouse novels with Michael Hordern as Jeeves.

Writing in The Guardian, critic Michael Coveney described Briers as "always the most modest and self-deprecating of actors, and the sweetest of men," and noted: "Although he excelled in the plays of Alan Ayckbourn, and became a national figure in his television sitcoms of the 1970s and 80s, notably The Good Life, he could mine hidden depths on stage, giving notable performances in Ibsen, Chekhov and, for Kenneth Branagh's Renaissance company, Shakespeare."

In a role specifically written for him by John Esmonde and Bob Larbey, Briers was cast in the lead role in The Good Life (1975–78), playing Tom Good, a draughtsman who decides, on his 40th birthday, to give up his job and try his hand at self-sufficiency, with the support of his wife Barbara, played by Felicity Kendal. Briers persuaded the producers to cast his friend Paul Eddington, a fellow council member of Equity, in the role of Jerry. An enormously successful series, the last episode in 1978 was performed in front of Queen Elizabeth II. In 1977, he starred with his The Good Life co-star Penelope Keith in the televised version of Alan Ayckbourn's trilogy The Norman Conquests. He also starred as Ralph in 13 episodes of The Other One (1977–79) with Michael Gambon.

During the 1980s and 1990s, Briers had leading roles in several television shows. including Goodbye, Mr Kent (1982), a rare failure also featuring Hannah Gordon, the lead role of Martin Bryce in Ever Decreasing Circles (1984–89), and as Godfrey Spry in the BBC comedy drama If You See God, Tell Him (1993). He also starred in All in Good Faith (1985), Tales of the Unexpected (1988), and Mr. Bean (1990). In 1987, he appeared as the principal villain in the Doctor Who serial Paradise Towers, a performance which was described by Radio Times Writer Patrick Mulkern as Briers' "career-low". In 1995 he played the character Tony Fairfax in the BBC comedy Down to Earth. In the Inspector Morse episode 'Death is Now My Neighbour', he played the evil master of Lonsdale College, Sir Clixby Bream.

Briers narrated numerous commercials. including adverts for the Midland Bank in which he was the voice of the company's Griffin symbol. Between 1984 and 1986 he made a series of commercials for the Ford Sierra done in a sitcom style portraying the Sierra as "one of the family". Briers notably narrated the public information film Frances the Firefly, about the dangers of playing with matches, firstly in the mid 1990s when first made, and then in the early 2000s when re-made by the Government fire safety campaign Fire Kills. He also recorded the voice of a Sat nav specifically designed for senior citizens in the BBC 2’s hit TV Show Top Gear, Series 19, episode 5, which aired only a week after his death. Presenter Jeremy Clarkson paid a brief tribute to his memory at the end of the episode.

Briers was a keen visitor of Britain's historic churches and visited over one hundred for his book English Country Churches which was published in 1988. From his national Service in the RAF, he was a supporter for a national memorial for RAF Bomber Command.

After a long career in television sitcom, and looking to expand his career, his daughter Lucy took him to Stratford-upon-Avon to watch Kenneth Branagh in Henry V. After meeting Branagh backstage after the performance, Branagh offered Briers the role of Malvolio in the Renaissance Theatre Company production of Twelfth Night. Briers joined the company, and went on to play title parts in King Lear and Uncle Vanya. Briers also appeared in many of Branagh's films, including Henry V (1989, as Bardolph), Much Ado About Nothing (1993, as Signor Leonato) and Hamlet (1996, as Polonius). The theatre production of Twelfth Night (1988) was adapted for television, with Briers reprising his role as Malvolio.

After 1990, he appeared in Lovejoy, Inspector Morse, Midsomer Murders (the episode "Death's Shadow"), Doctors, New Tricks, Kingdom, and If You See God, Tell Him. Richard Briers starred as Hector in the first three series of Monarch of the Glen from 2000 to 2002 (and as a guest in series 7 in 2005), a role which saw him return to the limelight. He contributed "Sonnet 55" to the 2002 compilation album, When Love Speaks, which features famous actors and Musicians interpreting Shakespeare's sonnets and play excerpts. In 2005, he appeared alongside Kevin Whately in Dad, a TV Film made by BBC Wales exploring issues of elder abuse. In 2006, he made an appearance in an episode of Extras, and portrayed the servant Adam in Kenneth Branagh's 2006 Shakespeare adaptation, As You Like It. He made a cameo appearance as a dying recluse in the 2008 Torchwood episode "A Day in the Death".

Briers and his friend Paul Eddington shared a similar sense of humour, and knew each other before being cast in The Good Life. After Eddington was diagnosed with skin cancer, Briers accepted a role opposite him in David Storey's play Home in 1994, agreeing to take on all of the publicity interviews to allow Eddington time for his treatment. At Eddington's memorial Service, Briers read both from Cymbeline and Wodehouse; he later read chapters from Eddington's autobiography on BBC Radio 4.

On 17 December 2000, Briers was the guest on BBC Radio 4’s Desert Island Discs. Among his musical choices were "Di quella pira" from Il Trovatore by Giuseppe Verdi, "I Feel A Song Coming On" by Al Jolson and "On The Sunny Side Of The Street" by Louis Armstrong. His favourite piece was the Organ Concerto in F major "The Cuckoo and the Nightingale" by George Frideric Handel. In 2012 he featured in the comedy-horror film Cockneys vs Zombies. In 2013, he did voice work for an episode of the motoring programme Top Gear, which aired one week after his death.

Interviewed by The Daily Telegraph in 2008, Briers admitted that, while on holiday, he enjoyed being recognised, saying, "I’m gregarious by nature, so I love chatting to people. It really cheers me up."

In 2010, Briers played in the Royal National Theatre revival of Dion Boucicault's London Assurance, alongside Simon Russell Beale and Fiona Shaw. A performance of this was broadcast live to cinemas round the world as part of the NT Live! programme.He also played the character of Captain Bluntschli, in Bernard Shaw's play 'Arms and the Man'

On Christmas Day 2013, BBC Radio 4 Extra broadcast a day of tribute to Briers titled "Ever Increasing Wonder", with a variety of his BBC Radio recordings, many of them introduced by those who knew him and worked with him. Guest speakers included:

In 2014, BBC Radio 4 broadcast Memories of a Cad, an affectionate comedy drama by Roy Smiles about the relationship between Terry-Thomas and Briers, played by Martin Jarvis and Alistair McGowan respectively. Set in 1984 when he had suffered from Parkinson's Disease for many years, Terry-Thomas is delighted by the visit to his home in Majorca of the much younger Briers, who he recognises from television, and who proves to be his first cousin once removed. Briers cheers him up by recalling the career the film-star has long forgotten. It was re-broadcast in 2016.