Petherbridge was born in West Bowling, Bradford, the younger son of William and Hannah Petherbridge. He attended Grange Grammar School, Bradford, where his favourite subjects were Art and English Literature. The composer Herbert Howells wrote of Petherbridge's boy soprano rendition, at the Wharfedale Festival, of Schubert's 'Trout': 'A fine young musician with a fine gift of word delivery.' Petherbridge trained as an actor at Esme Church's Northern Theatre School. At the time of national service in the 1950s, he was a conscientious objector. He made his professional stage debut at the Ludlow Festival in 1956, playing Gaveston in Marlowe's Edward II. His first London appearance was at the Open Air Theatre, Regent's Park in 1962 as Demetrius in A Midsummer Night's Dream.
Petherbridge began his tenure as part of Laurence Olivier's National Theatre Company in the 1960s, walking on in Olivier's Othello and later creating the role of Guildenstern in Tom Stoppard's Rosencrantz and Guildenstern Are Dead. He has been a leading actor in the Royal Shakespeare Company and Royal National Theatre; was a founding member of the Actors' Company in 1972; and with Ian McKellen established the McKellen-Petherbridge Group at the RNT in 1985.
He has been praised for both tragic and comic parts, interpreting a wide range of roles from Feydeau to Euripides. His major roles on stage include Newman Noggs in Nicholas Nickleby; Charlie Marsden in Strange Interlude; Gaev in The Cherry Orchard; the Cardinal in The Duchess of Malfi; Alceste in The Misanthrope; Frank Ford in The Merry Wives of Windsor; Malvolio in Twelfth Night, King Cymbeline in Cymbeline; Dr Dorn in The Seagull; Sir Anthony Blunt in Single Spies; the title role in 'Cyrano de Bergerac'; Krapp in Samuel Beckett's Krapp's Last Tape; Donner in Tom Stoppard's Artist Descending a Staircase; and Tiresias in Sophocles' Antigone.
Petherbridge has performed in stage musicals, including The Woman in White, Lost in the Stars, The Fantasticks, Coco, and, most recently, a musical version of The Importance of Being Earnest.
On television, he has made appearances in Journey's End, Maigret, Dead of Night, The Brief, Midsomer Murders (a role he took on after Ian Richardson died a few days before production was to begin), Land Girls and Doctors. His film roles include Richard St Ives in Mike Newell's An Awfully Big Adventure (1995), Dr. Pritchard in Gulliver's Travels (1996), Foster in A Christmas Carol (1999), Dom Vladimir in The Statement (2003), and Aesculapius in Pope Joan (2009), directed by Sonke Wortmann.
Petherbridge is a winner of the Olivier and London Theatre Critics' Awards (for his role as Charlie Marsden in Strange Interlude), and has twice been nominated for a Tony Award (for Nicholas Nickleby and Strange Interlude). He has also been a recipient of the Sony Award for Best Actor in a Radio Drama.
In 1989, Petherbridge was awarded an Honorary D.Litt. by the University of Bradford.
Petherbridge is married to the actress Emily Richard, with whom he has appeared several times on stage. They have two children, Dora (b. 1983) and Arthur (b. 1986). He has a son, David (b. 1965), by his first marriage to the New Zealand actress and director Louise Petherbridge (née Harris).
Petherbridge and his wife live in West Hampstead in North London. With his friend Kathleen Riley he is writing a history of West Hampstead, NW6 and All That.
In 2007, Petherbridge suffered two strokes while preparing to star in a production of King Lear. He later fictionalized the experience in the play My Perfect Mind, co-written with Kathryn Hunter.
His book, Slim Chances and Unscheduled Appearances was published in March 2011 and launched with a sell-out Platform at the National Theatre. At the same time he held his first art exhibition at Burgh House in Hampstead.
Petherbridge maintains a weekly blog, which often features his poetry, artwork and short films.
Petherbridge is the author of Pillar Talk (or Backcloth and Ashes), a one-man show about Saint Simeon Stylites, published in 2005. He has also contributed to The Continuum Companion to Twentieth-Century Theatre.
In 2011, Petherbridge published an autobiographical anthology of essays, poems and artwork under the title Slim Chances and Unscheduled Appearances, which includes a foreword by Sir Ian McKellen.