Lazenby was born in Queanbeyan, New South Wales, Australia. Before becoming an actor, Lazenby worked as an auto mechanic, car salesman and model. In 1968, Lazenby was cast as James Bond, despite his only previous acting experience being in commercials, and his only film appearance being a bit-part in a 1965 Italian-made Bond spoof, Espionage in Tangiers. Lazenby won the role based on a screen-test fight scene, the strength of his interviews, fight skills, and audition footage.

Although he had previously worked in television advertising and an Italian spy themed B-movie, Lazenby's first serious acting role was as James Bond in the film On Her Majesty's Secret Service (1969). Lazenby is the second actor to portray the British secret agent in a Bond feature film after Sean Connery, who had become a cultural icon in the role.

Connery quit the role in 1967, after five successful Bond films. In his place Albert R. Broccoli initially chose 21-year-old actor Timothy Dalton. However, Dalton declined, believing himself too young for the role. Harry Saltzman considered Roger Moore, but he was unavailable because of his television programme The Saint. Saltzman also briefly considered Jeremy Brett for the role of Bond after seeing his performance in My Fair Lady. The confirmed front runners were John Richardson, Hans de Vries, Robert Campbell and Anthony Rogers.

Broccoli chose Lazenby after seeing him in a commercial. Lazenby dressed the part by sporting several sartorial Bond elements such as a Rolex Submariner wristwatch and a Savile Row suit (ordered, but uncollected, by Connery). Broccoli offered him an audition. The position was consolidated when Lazenby accidentally punched a professional wrestler, who was acting as stunt coordinator, in the face, impressing Broccoli with his ability to display aggression. As a result, he was offered a contract for seven movies, but was convinced by his agent Ronan O'Rahilly that the secret agent would be archaic in the liberated 1970s and left the series in 1969. Lazenby's voice was dubbed over with George Baker's in scenes in which Bond impersonated Sir Hilary Bray (Baker's character), something not traditionally done with a leading actor whose original language is English. According to an interview, his difficulties stemmed from director Peter R. Hunt's refusal to speak directly with him, and brusqueness in asking Lazenby's friends to clear the set before filming.

At the time of the release of On Her Majesty's Secret Service (OHMSS), Lazenby's performance received mixed reviews. Some felt that whilst he was physically convincing, some of his costumes were inappropriate ("too loud" according to some) and that he delivered his lines poorly. Others however disagree and retrospectively as time has gone by, his performance is viewed far more favourably. In the 1998 book 'The Essential James Bond', Lee Pfeiffer & Dave Worrell write: "Although OHMSS was routinely dismissed by critics who cited Lazenby as a brave but disappointing successor to Connery, the intervening years have been notably kinder to both the film and its star. Indeed, due in no small part to Peter Hunt's inspired direction, OHMSS generally ranks among the top films with fans. Likewise, Lazenby has emerged as a very popular contributor to the series and has enjoyed large enthusiastic audiences during his appearances at Bond related events. In summary, OHMSS is a brilliant thriller in its own right and justifiably ranks amongst the best Bond films ever made".

In recent times when Roger Moore did commentary for a 2007 DVD release of The Man with the Golden Gun, he referenced George Lazenby as follows : "I have a great deal of e-mail contact with George Lazenby; he's sort of on the joke circuit ... that we simply send jokes to each other. OHMSS - very well made film - Peter Hunt - excellent, excellent, excellent fight stuff, excellent snow effects ... but I think the end result for George was that it was one of the better Bond's".

OHMSS also featured the only breaking of the "fourth wall" (the actor breaking the boundary between the setting and its audience) in the official EON-produced Bond series. (This also occurs in the unofficial film Never Say Never Again (1983) when Sean Connery winks to the audience). In the opening beach scene, just prior to introductory credits rolling, Lazenby cracks - in reference to Connery's Bond - "this never happened to the other fellow".

Lazenby has portrayed James Bond several times over the years in numerous parodies and unofficial 007 roles, most notably the 1983 TV movie The Return of the Man from U.N.C.L.E. and an episode of The New Alfred Hitchcock Presents, entitled "Diamonds Aren't Forever".

Lazenby has portrayed The Marlboro Man in cigarette advertising.

Despite starring in On Her Majesty's Secret Service and 1977's The Kentucky Fried Movie (the combined gross earnings of which exceeded $100 million worldwide in the 1970s, then the standard establishing an actor as a box office success), Lazenby's acting career did not flourish.