The recognition for his performance in the title role of Steven Spielberg's biopic of US President Abraham Lincoln puts him above Hollywood legends including Dustin Hoffman and Marlon Brando who both won it twice.
Accepting his award from Meryl Streep, Day-Lewis told the audience: "I really don't know how any of this happened."
Day-Lewis also paid tribute to his wife, before tearfully thanking his mother.
The other big winners on the night were Anne Hathaway, named best supporting actress for her role in Les Miserables, Jennifer Lawrence who won best actress and Ben Affleck's Argo which won best film.
Ang Lee was named best director for Life Of Pi, while Adele triumphed in the best original song category for her Bond theme Skyfall.
She thanked her songwriting partner Paul Epworth, who came on stage with her, for "believing in me all the time, and my man, I love you baby".
Earlier she had performed the song on stage at the Dolby Theatre in Hollywood - the first time she had ever sung it live.
Christopher Plummer presented the Oscar for best supporting actress to Hathaway.
Referring to her character Fantine, who was forced into prostitution, an emotional Hathaway said she hoped for a future in which "the misfortunes of Fantine will only be found in stories and nevermore in real life".
Lawrence, who stumbled on her way to the stage, said: "You guys are just standing up because you feel bad that I fell over and that's embarrassing.
"This is nuts."
The Oscar for best original score went to Mychael Danna for Life Of Pi, the Oscar for adapted screenplay went to Chris Terrio for Argo before the nominees for best film were introduced by first lady Michelle Obama from the White House.
Director and star Affleck paid tribute to the "genius" of Steven Spielberg whose film, Lincoln, was one of the ones that lost out.
Referring to his early success with the Oscar-winning Good Will Hunting, he said: "I never thought I would be back here and I am because of so many of you who are here tonight."
He added: "It doesn't matter how you get knocked down in life, all that matters is that you get up."
There were also wins for Quentin Tarantino's western Django Unchained with Christoph Waltz named best supporting actor, while Tarantino picked up the Oscar for original screenplay telling his fellow writers: "You guys are so wonderful. Peace out."
The show's host Seth MacFarlane, the man behind hit cartoon Family Guy, started proceedings by poking fun at the Academy for not nominating Affleck for his directing Argo which about a CIA scheme to free American hostages in Iran, saying the plan was "so top secret the film's director is unknown to the academy".
The award for best animated short film went to Disney's Paperman, meaning National Film and Television School students Timothy Reckart and Fodhla Cronin O'Reilly missed out on an Oscar.
The Oscar for animated feature film went to Brave - a cartoon set in the Scottish Highlands and featuring the voices of Billy Connolly, Emma Thompson and Julie Walters.
The prize for cinematography went to Claudio Miranda for Life Of Pi with the film, based on Yann Martel's award-winning novel, also picking up the Oscar for visual effects.
The award for costume design went to Jacqueline Durran for Anna Karenina.
The British designer said the win was "completely overwhelming" and paid tribute to her children who were "fast asleep in England".
There was another UK win when the Oscar for makeup and hairstyling was won by Lisa Westcott and Julie Dartnell for Les Miserables.
Halle Berry - a one-time Bond girl - introduced a tribute to the Bond films and music made up of classic clips of 007's adventures which continued with Dame Shirley Bassey singing the theme to the 1964 film Goldfinger which was given a standing ovation from the assembled stars.
The Oscar for best live action short film was won by Shawn Christensen for Curfew, while Inocente was named best short documentary.
Affleck presented the Oscar for documentary feature to Malik Bendjelloul and Simon Chinn for Searching For Sugar Man about the search for an ageing rock star who dropped out of sight before his career took off.
The Oscar for foreign language film went to the Austrian film Amour.
Saturday Night Fever star John Travolta then introduced a celebration of movie musicals which featured clips from Chicago before one of its stars, Catherine Zeta Jones, appeared on stage to sing All That Jazz.
She was followed by DreamGirls star Jennifer Hudson and then members of the cast of Les Miserables, including Hathaway, Eddie Redmayne and Hugh Jackman, performed One Day More from the hit film.
The film, based on Victor Hugo's novel, won the Oscar for best sound mixing.
There was a rare event - a tie - when the Oscar for best sound editing was shared between Zero Dark Thirty and Skyfall.
Sandra Bullock presented the Oscar for film editing to William Goldenberg for Argo, before Kristen Stewart and Daniel Radcliffe presented the Oscar for production design to Lincoln
George Clooney introduced a montage of clips dedicated to members of the film industry who died in the last 12 months including Tony Scott, Herbert Lom and Hal David.
Barbra Streisand paid tribute to composer Marvin Hamlisch with a performance of The Way We Were - which he wrote for her to sing in the 1973 film of the same name.