The 41-year-old was named best actor at the 88th Academy Awards, with Brie Larson named best actress Oscar for Room.
Spotlight took home the best picture Oscar with Mad Max: Fury Road picking up the most awards of the night, with six accolades.
Mark Rylance won the best supporting actor Oscar, and Sam Smith won best original song.
The ceremony had been boycotted by some Hollywood figures protesting about the lack of ethnic diversity among this year’s nominees, as all 20 nominees in the best acting or supporting acting categories are white.
Host Chris Rock addressed the controversy head on as he launched the ceremony, and it was a theme that was returned to several times during the night.
Chris Rock commented he had “counted at least 15 black people” in the montage that opened the ceremony, before welcoming people to the “white People’s Choice awards”.
The Revenant won three of the 12 awards for which it was nominated. Alejandro Inarritu also won best director and Emmanuel Lubezki won his third Oscar for cinematography in a row, having won in 2015 for Birdman and 2014 for Gravity.
Leonardo DiCaprio received a standing ovation as he picked up his award, after five acting nominations and one nomination as producer of best picture nominee Wolf of Wall Street.
He thanked his director and co-star Tom Hardy for his “fierce talent on screen” and “friendship off screen” before campaigning for action to combat climate change, saying making The Revenant was “about man’s relationship to the natural world”.
He asked the audience to “support leaders around the world who do not speak for the big polluters or the big corporations but who speak for all of humanity, for the indigenous people of the world, for the billions and billions of underprivileged people who’ll be affected by this”.
It is 22 years since Leonardo DiCaprio was first nominated for an Academy Award, having been nominated for best supporting actor for What’s Eating Gilbert Grape.
Speaking to reporters after his win, Leonardo DiCaprio said: “I feel very honored, to share this has been an amazing experience, to sit there and talk about the film.
“I also got to talk about something I have been obsessed with – the environment and climate change – on a platform with hundreds of millions of people watching worldwide.”
As he accepted his award, Alejandro Inarritu said it was a “great opportunity to our generation to liberate ourselves from all prejudice”, saying the color of someone’s skin should be “as irrelevant as the length of their hair”.
It is the fourth Oscar for Alejandro Inarritu, having won best director, best original screenplay (as co-writer) and best picture (as producer) for Birdman in 2015.
Brie Larson had won praise for her role as abducted woman Ma in Room, based on the book by Emma Donoghue.
The actress thanked everyone involved in the film, including young co-star Jacob Tremblay, who plays her son.
Spotlight tells the true story of how investigative reporters at the Boston Globe uncovered child abuse by Catholic priests in Massachusetts.
Mark Rylance won his Oscar for Steven Spielberg’s Cold War film Bridge of Spies, in which he plays Rudolf Abel, the real-life Soviet intelligence officer who was arrested in 1950s New York and prosecuted as a spy.
Sam Smith, whose song was featured in Bond film SPECTRE, told the audience at LA’s Dolby Theater he could not breathe as he picked up his award and described his fellow nominees as “incredible”.
Alicia Vikander won the best supporting actress Oscar for The Danish Girl.
The Swedish-born actress thanked her co-star Eddie Redmayne and her parents, after winning her first Oscar, saying: “Eddie, thank you for being the best acting partner. I could never have done it without you. You raised my game.
“My mum and dad, thank you for giving me the belief that anything can happen – even though I would never have believed this.”
Amy Winehouse documentary Amy won the best documentary feature Oscar for British filmmakers Asif Kapadia and James Gay-Rees.
Composer Ennio Morricone won the Oscar for best original film score for The Hateful Eight – the first Academy Award the 87-year-old has won in his career.
Irish director Benjamin Cleary and Serena Armitage won the best live action short Oscar for Stutterer, about a man with a severe stammer.
The best foreign language film Oscar went to Hungarian film Son of Saul, telling the story of a Jewish man forced to work at a Nazi death camp who seeks a proper religious burial for a boy who he believes is his son.
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