Pleasence was born, the son of Alice (née Armitage) and Thomas Stanley Pleasence, a stationmaster. He was brought up in the small village of Grimoldby, Lincolnshire, and attended Ecclesfield Grammar School, in south west Yorkshire.

His acting career began in a production of Wuthering Heights, but was interrupted by World War II. He was at first a conscientious objector, but later joined the Royal Air Force and served with 166 Squadron, Bomber Command. His Avro Lancaster was shot down on 31 August 1944 during a raid on Agenville.

He was taken prisoner and tortured by his captors then placed in a German prisoner-of-war camp, where he produced and acted in plays. He would later play Flight Lt. Colin Blythe in The Great Escape where much of the story takes place inside a POW camp.

Pleasence returned to acting after the war, and critics began to call him the "Man with the Hypnotic Eye". Coupled with his bald head and quiet but intense voice, he specialized in insane and evil characters, including Prince John in the ITV series The Adventures of Robin Hood, Heinrich Himmler in The Eagle Has Landed, and the Bond villain Blofeld in You Only Live Twice. In his later years, he became known to a younger generation as Dr. Loomis in Halloween. His trademark voice may be credited to elocution lessons he had as a child.

In the early 1960's, he recorded several children story records on the Atlas Record label under the Talespinners series in the U.K., later released in the U.S. as Tale Spinners For Children on the United Artist label. The stories included were Don Quixote and the Brave Little Tailor.

Perhaps his most sympathetic role was as the tragic POW Colin Blythe in the 1963 film The Great Escape, who discovers he is slowly going blind, but nonetheless participates in the escape, and is shot down by Nazi officers because he is unable to see them.

One of his earliest roles on television, as Syme in the BBC's highly-acclaimed 1954 adaptation of George Orwell's novel Nineteen Eighty-Four, also starred Peter Cushing - another actor who would go on to find fame in many horror film roles.

He appeared twice with Patrick McGoohan in the British spy series, Danger Man, in episodes "Find and Return" and "Position of Trust". His first appearance in America was in an episode of The Twilight Zone, He played an aging (and suicidal) teacher at a boys' school in the 1962 episode "The Changing of the Guard".

He hosted the 1981 Halloween episode of Saturday Night Live with music guest Fear (which, because of Fear's raucous performance and the sick, dark humor of the sketches, hasn't been seen on television since its first airing)

Pleasence starred as Rev. Septimus Harding in the BBC's 1982 production of The Barchester Chronicles. He played the murderer in an episode of Columbo entitled "Any Old Port in a Storm" and also had the distinction of having been a culprit captured by Mrs. Columbo in "Murder is a Parlor Game."

Pleasence also provided the voiceover for the British Public Information Film, The Spirit of Dark and Lonely Water. The film, intended to warn children of the dangers of playing near water, attained notoriety for allegedly giving children nightmares.

His acting hero was Sir Laurence Olivier whom he worked with many times, including the 1979 version of Dracula. Pleasence even does an amusingly broad impersonation of Olivier as horror film actor "Valentine De'ath" in the 1977 film The Uncanny.

Pleasence was nominated twice for the Tony award for best performance by a leading actor in a play: in 1969 for The Man in the Glass Booth, and in 1972 for Wise Child; and he was awarded an OBE in 1994.