Payne continued school studies, despite a contact with a talent scout during that time. After his graduation, he enrolled in the National Youth Theatre for two seasons. Payne has described this experience as "Four hundred kids thrown together to work on 7 plays." In addition, he was occupied with the Edinburgh Festival Fringe for one season. He then auditioned for several fringe acting companies, but was told he was too young and lacked experience. However, in 1979, he was admitted to the "prestigious" RADA acting programme. Before being accepted at RADA, Payne worked as a joiner, a salesman, and a landscape gardener. Payne graduated from RADA in 1981 with seven major prizes for acting, comedy (Payne won the Fabia Drake Prize for Comedy) and physical presence.

Payne was part of a 'new wave' of actors to emerge from the academy. Others included Jonathan Pryce, Juliet Stevenson, Alan Rickman, Anton Lesser, Kenneth Branagh, and Fiona Shaw. In 1980 the Principal of RADA, Hugh Cruttwell, selected a scene from an adaptation of william Shakespeare's Macbeth, which Payne co-wrote with Paul McGann, to be performed in front of Queen Elizabeth II, in one of her rare visits to the academy. Payne directed the scene in which he and McGann acted. Payne played Macbeth and wielded a baseball bat on stage instead of a sword. Kenneth Branagh performed a soliloquy from Hamlet at the same event.

In 1983, he appeared in Michael Mann's horror film The Keep as an unnamed border guard. That same year, Steven Berkoff cast him in his production of West at the Donmar Warehouse. Payne played Les, a member of an East End London gang intent on gaining revenge against the rival Hoxton Mob for the slaying of one of their number. Richard Corliss of TIME stated that Payne bestowed "a frighteningly dynamic performance" in the play.

In 1985, Payne was cast as a "committed", "butch snooker manager" known as "The One" (also known as "T.O.") in Director Alan Clarke's snooker musical Billy the Kid and the Green Baize Vampire. Michael Brooke stated that Payne gave the "stand-out performance" in the film. and MS London stated that Payne 'is a charismatic presence, with a capable voice, who is perfectly cast as The One'.

In 1986, both Payne and Berkoff appeared in Julien Temple's musical Absolute Beginners . Payne played a psychotic "pompous and pathetic racist" named Flikker, who participated in the 1958 Notting Hill race riots. One reviewer argued that Payne was "the only actor to walk off Absolute Beginners with his reputation not only intact but enhanced" and that his portrayal of Flikker "was a headbutt of reality in a fantasmagoria of overkill." One critic stated that Payne gave a "meaty, saving-grace performance" in the film. The film Journalist and Editor, Ann Lloyd, selected Payne as the most promising newcomer of 1987 for his role in the film. In the same year Payne appeared in the Mel Brooks film Solarbabies, along with fellow British performer Alexei Sayle, as filthy bounty Hunters named Dogger and Malice. Payne said of his and Sayle's performances in Vogue that "the old image of an English arch-villain – Boris Karloff, that sort of thing" is turned "upside down. We're just a couple of soaks".

In 1988, Payne appeared as Eddy in the Steven Berkoff-directed play, Greek (a retelling of Sophocles' Oedipus Rex), at the Wyndham's Theatre. Martin Hoyle, writing for The Independent, stated that Payne's "Eddy is vital, intelligent and physically disciplined in the best Berkoff style". Charles Osbourne, writing for The Daily Telegraph, stated that Payne brought "a cheerful zest to the role of Eddy".

In 1989, he was cast in For Queen and Country as a 'drug kingpin' named Colin.

In 1990 Payne appeared in the music video for Neil Young's song Over and Over, directed by Julien Temple, as a Stanley Kowalski (played by Marlon Brando in A Streetcar Named Desire, a film based on Tennessee Williams' play of the same name) esque character.

In 1991, Payne was cast as the Devil in Switch. Payne was described as a "delightfully wicked Satan" by Film Review. The Providence Journal described him as a "slick devil".

In 1992, Payne was cast in his best-known role, opposite Wesley Snipes, as a "notorious terrorist and hijacker", with a steely, demonic nerve, named Charles Rane, in Passenger 57. Marcus Trower of Empire stated that Payne was "a brilliantly disconcerting MadMan. With his flowing blond Jesus locks, armour-piercing stare and Casual sadism, he makes Hannibal Lecter look like a social worker – and like Anthony Hopkins' serial killer, part of the man's menace is in the apparent contradiction between his articulate, well-spoken English and his off-hand brutality." The Radio Times stated that Payne and Snipes both gave "charismatic turns" in the film. The New York Times stated that Payne brought a 'tongue-in-cheek humor to the psychopathic fiend'. A reviewer for People magazine stated that "Bruce Payne steals the plane—and the movie". In an article for the Waterloo Region Record, Jamie Portman described Payne as a "suave and cultivated English actor" playing "a suave and cultivated killer named Charles Rane" and suggested that a "key reason Director Kevin Hooks chose him for the role was that he wanted a villain with as much magnetism as the hero". Payne was described as "icily perfect as the villainous Rane" in the Worcester Telegram & Gazette. Julius Marshall stated that Payne was "ideal for his role: charming, dangerous – the kind of evil genius you love to hate". The Star Tribune stated that 'Bruce Payne makes a splendid psychopath, consistently stealing scenes from the likes of Wesley Snipes and Elizabeth Hurley throughout Passenger 57'.

In 1993, Payne played a "charismatic" werewolf named Adam Garou in Full Eclipse. Joseph Savitski, who reviewed the film for Beyond Hollywood, stated, "Payne is masterful as Detective Garou, a seductive and evil villain with arrogance and confidence to spare. When he's on screen, Payne demands the attention of the audience, and you're hard pressed to resist his performance. Payne is also the perfect adversary, the kind you're supposed to hate, but who has the charisma to draw you in nonetheless".

In 1995, Payne played a "rogue FBI agent" named Karl Savak in Director Kurt Wimmer's One Tough Bastard. One reviewer described Savak as one of the most 'entertaining movie villains in low budget action flick history' and noted that 'so awesome is Karl Savak that some lunatic has created a Facebook page in his honor'. Another reviewer stated that 'Bruce Payne, with his Whitesnake hair and nose ring is slimeball perfection as the villain'. In 1998, he played Jurgen, a first-class and charismatic operative in season two of La Femme Nikita.

In 2000, Payne portrayed the villain Jacob Kell in Highlander: Endgame (2000), the third sequel to the original Highlander film. One reviewer said of Highlander: Endgame, "the one in the cast that seems to be having the most fun is Bruce Payne. Traditionally, Highlander villains give performances that go completely over-the-top and well into the stratosphere. Payne contrarily gives a performance where he enunciates every syllable with relish and dramatic weight, resulting in a performance that is entirely captivating whenever he is on screen."

Payne was born in Woking, Surrey, and grew up in New Haw, Surrey. He developed an interest for acting at an early age. In an interview with Impact magazine in 2001, Payne revealed, "I know that my immediate family tell me that when I was very young I saw a play that my brother was in – probably a Peter Pan pantomime because it involved a crocodile – and I apparently shouted out 'That crocodile is going to eat my brother' and ran up on the stage. I don't remember that myself, but if it really happened, I think it shows that from an early age I loved that suspension of disbelief".

In 2004, Payne appeared as the "snarling" Neighbour, who "dabbles" in producing kinky virtual games in the dystopian horror mystery Paranoia 1.0. The film was nominated in the best film category at the Sitges - Catalan International Film Festival and at the Sundance Film Festival, and won the best film award at the Malaga International Week of Fantastic Cinema. John Fallon stated that as the Neighbour, Payne "laid on the charisma and the macho-ness thick".

In November 2005, Payne was arrested at Heathrow Airport after disembarking a FLIGHT from Los Angeles and was later cautioned for using "threatening behaviour". Payne's Lawyer stated that Payne had simply argued with another Passenger who refused to stop using his mobile phone after being asked to do so by FLIGHT crew.

In 2006, he helped to launch the National Youth Theatre's 50th-anniversary programme along with Sir Ian McKellen, Timothy Spall, Diana Quick, Paula Wilcox, Jonathan Wrather, newsreader Krishnan Guru-Murthy, and Little Britain's Matt Lucas and David Walliams.

In 2011, Payne appeared in the horror film Prowl as a "blatantly untrustworthy" "hillbilly truck driver" named Bernard in the film. Matt Withers, who reviewed the film for JoBlo.com, stated that "Bruce Payne shows up as a trucker in a throwaway role that he makes anything but". Payne also appeared in Carmen's Kiss (an adaptation of the Georges Bizet opera Carmen).

In 2012, Payne voiced a demon in the found-footage horror film Greystone Park (also known as The Asylum Tapes).

In 2013, Payne appeared in the Warner Bros. action film Getaway. Payne also appeared in the action film Vendetta as a sinister Whitehall Mandarin named Mr. Rooker. One reviewer of the film gave it eight out of ten and stated that Payne 'nearly steals the movie with a plum role as the icy head of British black ops'. In addition, Payne portrayed Auschwitz camp Commandant Rudolf Hoess, in a 'superciliously evil' manner, in the French film Victor Young Perez, which concerns the life of the Tunisian Jew flyweight boxer Victor Perez.

In 2015, Payne played Winston, a religious fanatic, in the horror film Re-Kill.

In 2018 Payne appeared in the Anthology film London Unplugged, which premiered at the East End Film Festival. In addition, Payne played the main antagonist in Creators: The Past (which he also produced and acted as assistant Director for), which is due to be released in 2018. Payne has also been cast as Frank Warren in Michael-The Michael Watson Story, a biopic of boxer Michael Watson.