The Canadian-born actor passed away in hospital in Fort Lauderdale, Florida, where he was being treated for pneumonia, his agent John S Kelly said.
The "Laurence Olivier of Spoofs" came late to comedy after spending decades as a straight actor in TV dramas during the 1950s.
Over the course of his six decade career Nielsen - who was 6ft 2ins - appeared in over 100 films and 1,500 television shows, portraying more than 220 characters.
Born of a Welsh immigrant mother and Danish-born Canadian Mountie in Saskatchewan, Canada, Nielsen suffered an abusive childhood at the hands of his father.
Seeking to escape, he was heavily influenced by his half-uncle Jean Hersholt, a prominent silent film actor, but eventually enlisted in the Royal Canadian Air Force where he trained as an aerial gunner.
He briefly worked as a disc jockey at a radio station in Calgary, Alberta, before enrolling at Toronto's Lorne Green Academy of Radio Arts and later receiving a scholarship from New York's Neighbourhood Playhouse.
Nielsen also attended the Actor's Studio and made his first TV appearance in 1948 opposite Charlton Heston in an episode of Studio One for which he was paid $75.
He later made a success of drama roles - appearing in almost 50 live programmes in 1950 alone - and made his big screen debut in the Michael Curtiz-directed musical film The Vagabond King.
Nielsen caught the eye of producer Nicholas Nayfack who offered him a role in the science fiction film Forbidden Planet, which is regarded as the forerunner of Star Trek.
The film was a success and Nielsen went on to star in subsequent movies such as Ransom!, The Opposite Sex and Hot Summer Night and the lead role opposite Debbie Reynolds in the romantic comedy Tammy and the Bachelor.
He missed out on the role of Messala in 1959's Ben Hur (also starring Heston) but landed the lead role in the Disney mini-series The Swamp Fox, as American Revolutionary War hero Francis Marion.
Subsequent roles included the captain in disaster movie The Poseidon Adventure and appearances in cop shows such as Kojak, Cannon, Ironside and Hawaii Five-O.
Nielsen's comedic breakthrough came with a supporting role in 1980's Airplane!, a parody of Zero Hour!, Airport, and other high concept disaster movies.
In Airplane! his deadpan delivery contrasted with the continual absurdity surrounding him: asked, "Surely you can't be serious?", he responds with a curt, "I am serious. And don't call me Shirley."
The film's success persuaded the directors - im Abrahams, David Zucker, and Jerry Zucker - to translate its comedy flavour to TV, casting Nielsen in the lead role in their new series, Police Squad!.
The series introduced Nielsen as Frank Drebin, the stereotypical bumbling police officer modelled after characters in earlier police TV series such as M Squad, Cannon and The Streets of San Francisco.
However, six years after the cancellation of Police Squad, the makers decided to make a feature length version with Nielsen reprising the role of Frank Drebin in The Naked Gun: From the Files of Police Squad!.
Even a leading role in a Mel Brooks comic horror parody, Dracula: Dead and Loving It, failed to generate much box office excitement although it did gain a following on its later release to video.
Both 1996's Spy Hard and 1998's Wrongfully Accused, a parody of The Fugitive, received even more popularity on home video but were not-well received by critics.
His first major slapstick success since The Naked Gun came in a supporting role in Scary Movie 3 as President Harris, a role he would reprise in the inevitable sequel Scary Movie 4.
(Nielsen appeared almost fully nude, prompting one critic to refer to the scene as putting "the 'scary' in Scary Movie 4.").
Even in his eighties, Nielsen continued to have an active career with performances on screen and stage as well as providing voice-overs and on-camera appearances for commercials.
In November 2010, Nielsen was admitted to a Fort Lauderdale, Florida hospital for pneumonia and died on November 28 surrounded by family and friends.
Sky Movies will be having a Leslie Nielsen tribute night on Sky Movies Comedy/HD on Saturday December 4 featuring all three Naked Gun movies as well as Airplane!
18.30 The Naked Gun
20.00 The Naked Gun 2 1/2: The Smell Of Fear
21.30 The Naked Gun 33 1/3: The Final Insult