Redgrave made his first professional appearance at the Playhouse in Liverpool on 30 August 1934 as Roy Darwin in Counsellor-at-Law (by Elmer Rice), then spent two years with its Liverpool Repertory Company where he met his Future wife Rachel Kempson. They married on 18 July 1935.

His plays include The Seventh Man and Circus Boy, both performed at the Liverpool Playhouse in 1935, and his adaptations of A Woman in Love (Amourese) at the Embassy Theatre in 1949 and the Henry James novella The Aspern Papers at the Queen's Theatre in 1959.

Offered a job by Tyrone Guthrie, Redgrave made his first professional debut in London at the Old Vic on 14 September 1936, playing Ferdinand in Love's Labours Lost. During 1936–37 he also played Mr Horner in The Country Wife, Orlando in As You Like It, Warbeck in The Witch of Edmonton and Laertes to Laurence Olivier's Hamlet. His hit of the season was Orlando. Edith Evans was his Rosalind and the two fell very much in love. As he later explained: "Edith always had a habit of falling in love with her leading men; with us it just went rather further." As You Like It transferred to the New Theatre in February 1937 and Redgrave again played Orlando.

Redgrave owned White Roding Windmill from 1937 to 1946. He and his family lived in "Bedford House" on Chiswick Mall from 1945 to 1954. His entry for Who's Who in the Theatre (1981) gives his address as Wilks Water, Odiham, Hampshire.

A card was found among Redgrave's effects after his death. The card was signed "Tommy, Liverpool, January 1940", and on it were the words (quoted from W.H. Auden): "The word is love. Surely one fearless kiss would cure the million fevers".

Redgrave joined the Royal Navy as an ordinary seaman in July 1941, (HMS Illustrious) but was discharged on medical grounds in November 1942. Having spent most of 1942 in the Reserve he managed to direct Lifeline (Norman Armstrong) starring Frank Pettingell at the Duchess Theatre in July; and The Duke in Darkness (Patrick Hamilton) starring Leslie Banks at the St James's Theatre in October, also taking the role of Gribaud.

His first American film role was opposite Rosalind Russell in Mourning Becomes Electra (1947), for which he was nominated for an Academy Award for Best Actor. In 1951 he starred in The Browning Version, from Sir Terrence Rattigan's play of the same name. The Daily Mirror described Redgrave's performance as Crocker-Harris as "one of the greatest performances ever seen in films". The 1950s also saw Redgrave in The Importance of Being Earnest (1952), The Dambusters (1954) with his portrayal of the Inventor Barnes Wallis, 1984 (1956), Time Without Pity (1957), for which he was nominated for a BAFTA Award, and The Quiet American (1958).

During the filming of Fritz Lang's Secret Beyond the Door (1948), Redgrave met Bob Michell. They became lovers. Michell set up house close to the Redgraves, and he became a surrogate "uncle" to Redgrave's children (then aged 11, 9 and 5), who adored him. Michell later had children of his own, including a son he named Michael. Fred Sadoff was an actor/director who became Redgrave's assistant and lover; they shared lodgings in New York and London.

Joining the Old Vic Company at the New Theatre for its 1949–50 season, he played:

In 1951 Redgrave received the Best Actor Award (Cannes Film Festival) for The Browning Version. Redgrave twice (1958 and 1963) won Best Actor trophies in the Evening Standard Awards and twice received the Variety Club of Great Britain 'Actor of the Year' award (in the same years).

He was appointed Commander of the Order of the British Empire (CBE) in 1952 and was knighted in 1959. He was also appointed Commander of the Order of the Dannebrog, Denmark in 1955.

Redgrave became the First President of the English Speaking Board in 1953, and President of the Questors Theatre, Ealing in 1958.

At the Apollo in June 1955 he played Hector in Tiger at the Gates, appearing in the same role at the Plymouth Theatre, New York City in October 1955 for which he received the New York Critics' Award. While in New York he directed A Month in the Country at the Phoenix Theatre in April 1956, and directed and played the Prince Regent in The Sleeping Prince at the Coronet Theatre in November 1956.

Returning to London in January 1958, Redgrave appeared as Philip Lester in A Touch of the Sun (N. C. Hunter) at the Saville Theatre. He won Best Actor in the Evening Standard Awards 1958 for this role. He rejoined the Shakespeare Memorial Theatre Company in June 1958, to play Hamlet and Benedick, also playing Hamlet with the company in Leningrad and Moscow in December 1958. (His wife Rachel Kempson played Ursula in Much Ado About Nothing and Lady Capulet in Romeo and Juliet).

At the Queen's Theatre in London in August 1959, he played H.J. in his own adaptation of the Henry James novella The Aspern Papers. His play was later successfully revived on Broadway in 1962, with Dame Wendy Hiller and Maurice Evans. The 1984 London revival featured his daughter, Vanessa Redgrave, along with Christopher Reeve and Hiller, this time in the role of Miss Bordereau.

Returning to Britain, in July 1962 he took part in the Chichester Festival Theatre's opening season, playing the title role in Chekhov's Uncle Vanya to the Astrov of Laurence Olivier who also directed.

Redgrave played (and co-presented) Lancelot Dodd MA in Arthur Watkyn's Out of Bounds at Wyndham's Theatre in November 1962, following it at the Old Vic with his portrayal of Claudius opposite the Hamlet of Peter O'Toole on 22 October 1963. This Hamlet was in fact the National Theatre's official opening production, directed by Olivier, but Simon Callow has dubbed it "slow, solemn, long", while Ken Campbell vividly described it as "brochure theatre."

Notable television performances include narration for The Great War (1964), a history of the First World War using stills and 'stretched' archive film, and the less successful Lost Peace series (BBC Television, 1964 and 1966). Of the latter, Philip Purser wrote: "The commentary, spoken by Sir Michael Redgrave, took on an unremittingly pessimistic tone from the outset."

In May and June 1965 Redgrave directed the opening festival of the Yvonne Arnaud Theatre in Guildford, including directing and playing Rakitin in A Month in the Country (co-starring with Ingrid Bergman as Natalya Petrovna), and Samson in Samson Agonistes (co-starring with Rachel Kempson as Chorus). He again played Rakitin in September 1965, when his production transferred to the Cambridge Theatre in London. For the Glyndebourne Festival Opera he directed Werther in 1966 and La bohème in 1967.

In 1966, he received an honorary DLitt degree from the University of Bristol.

At the Mermaid Theatre in July 1971 he played Mr Jaraby in The Old Boys (William Trevor) and had an unfortunate experience: "My memory went, and on the first night they made me wear a deaf aid to hear some lines from the prompter and it literally fell to pieces – there were little bits of machinery all over the floor, so I then knew I really couldn't go on, at least not learning new plays."

Nevertheless, he successfully took over the part of Father in John Mortimer's A Voyage Round My Father at the Theatre Royal, Haymarket, also touring Canada and Australia in the role in 1972–73. International touring continued in 1974–75 with a Royal Shakespeare Company production of The Hollow Crown, visiting major venues in the USA, New Zealand and Australia, while in 1976–77 he toured South America, Canada and the UK in the anthology, Shakespeare's People.

The Redgrave Theatre in Farnham, Surrey, 1974–1998, was named in his honour.

His final work, in 1975, a narrative of the epic poem, The Rime of the Ancient Mariner, by Samuel Taylor Coleridge, a poem that Redgrave taught as a young schoolmaster and visualised by producer-director Raul da Silva, received six international film festival prizes of which five were first place in category. This work was to be his last before the onslaught of Parkinson's disease.

In 1976, after suffering symptoms for many years, Redgrave was diagnosed with rapidly advancing Parkinson's disease. He began a regimen of therapies and medications that caused disorientation and other side effects. Costs for his Health care expenses and his diminished earning power caused the family to apply for public assistance from the King George's Pension Fund. In an interview on his seventieth birthday, he said: "For a long time, nobody understood the Parkinson's condition, and Directors thought I was just forgetful or drunk--and even now the work isn't easy. The difficulty is not just remembering lines but getting from place to place."

Redgrave's final theatre appearance came in May 1979 when he portrayed Jasper in Simon Gray's Close of Play, directed on the Lyttelton stage at the National Theatre by Harold Pinter. It was a silent, seated role, based on Gray's own father, who had died a year before he wrote the play. As Gray has said: "Jasper is in fact dead but is forced to endure, as if alive, a traditional English Sunday, helpless in his favourite armchair as his three sons and their wives fall to pieces in the usual English middle class style, sometimes blaming him, sometimes appealing to him for help and sobbing at his feet for forgiveness, but basically ignoring him. In other words I had stuck him in Hell, which turns out to be 'life, old life itself'."

Redgrave died in a nursing home in Denham, Buckinghamshire on 21 March 1985, from Parkinson's disease, one day after his 77th birthday. He was cremated at Mortlake Crematorium and his ashes were scattered in the garden of St Paul's, Covent Garden (The Actors’ Church), London.

In 1986, he was inducted posthumously into the American Theater Hall of Fame.

The 1996 BBC documentary film Michael Redgrave: My Father, narrated by Corin Redgrave, and based on his book of the same name, discusses the older actor's bisexuality in some depth. Rachel Kempson recounted that, when she proposed to him, Redgrave said that there were "difficulties to do with his nature, and that he felt he ought not to marry". She said that she understood, it didn't matter and that she loved him. To this, Redgrave replied, "Very well. If you're sure, we will".

Corin helped his father in the writing of his last autobiography. During one of Corin's visits to his father, the latter said, "There is something I ought to tell you". Then, after a very long pause, "I am, to say the least of it, bisexual". Corin encouraged him to acknowledge his bisexuality in the book. Michael agreed to do so, but in the end he chose to remain silent about it. Alan Strachan's 2004 biography of Redgrave discusses his affairs with both men and women. Although Redgrave had some long-term relationships with men, he also was prone to cruising Victoria or Knightsbridge for what he called "a necessary degradation", a habit of quick pick-ups that left him with a lasting sense of self-disgust.