The 41-year-old started acting in commercials when he was 14 and soon made his mark on TV shows.
The actor landed his first Oscar nomination when he was 19 and shot to superstardom, causing "Leo Mania" with his portrayal of Jack Dawson in "Titanic."
Since then, he's earned a total of six nominations, but has still come up short. His snubs have become a running joke among fans. Some have created "Sad Leo" memes, and one fan even created a computer game devoted to the subject.
But with his portrayal of Hugh Glass in "The Revenant," it looks like this might be the year DiCaprio snags the elusive — and well-deserved — Oscar. He's currently heavily favored to win.
With the Oscars taking place February 28, here's a look back at his memorable career:
Leonardo DiCaprio began his career acting in television ads, particularly after landing one for Matchbox cars when he was 14.
His first role was in the direct-to-video film "Critters 3," and he soon landed TV roles in the short-lived series "Parenthood," based on the movie of the same name, and other series, including "The New Lassie," "Santa Barbara," and "Roseanne."
He gained attention for his recurring role as a homeless kid in "Growing Pains" during the sitcom's seventh and final season.
Soon after that, Robert De Niro handpicked DiCaprio to play the lead in "This Boy's Life." This was DiCaprio's big-screen debut.
But it was his next role starring as the developmentally disabled brother in "What's Eating Gilbert Grape" that earned him critical praise and landed him his first Oscar nomination. He was 19.
In 1995, he appeared in the western "The Quick and the Dead," as French poet Arthur Rimbaud in "Total Eclipse," and as a young drug addict in "The Basketball Diaries."
He dived into romances with "Romeo + Juliet," Baz Luhrmann's 1996 modern take on Shakespeare's classic romantic tragedy.
It was his role as Jack Dawson in David Cameron's "Titanic" that catapulted him to superstardom. The film is the second-highest grossing worldwide, but according to Cameron, DiCaprio needed some convincing to take the role.
DiCaprio tackled a few more roles, including "The Man in the Iron Mask" and "The Beach," before landing the lead opposite Tom Hanks in Stephen Spielberg's "Catch Me If You Can" and earning his third Golden Globe nomination.
"Catch Me If You Can."
That same year, he starred in "Gangs of New York." The film would mark DiCaprio's first collaboration with director Martin Scorsese.
DiCaprio founded Appian Way Productions, and the company's first film was 2004's "The Assassination of Richard Nixon." The next was the 2004 biopic "The Aviator," starring DiCaprio.
Scorsese and DiCaprio teamed up again for "The Aviator." DiCaprio earned his first lead-actor Oscar nomination — his second in total — for his portrayal of Howard Hughes. He won his first Golden Globe for the role.
In 2007, he narrated, cowrote, and coproduced "The 11th Hour," a documentary examining the state of the environment.
"The Departed" in 2006 saw Scorsese and DiCaprio back together. The actor earned a Golden Globe nomination for his portrayal of a cop who infiltrates a criminal organization.
He earned another Golden Globe nomination for "Blood Diamond" from that same year. His portrayal of a diamond smuggler landed him his third Oscar nomination.
He reunited with his "Titanic" costar, Kate Winslet, for 2008's "Revolutionary Road." The film earned critical praise and garnered DiCaprio his seventh Golden Globe nomination.
DiCaprio took on psychological films in 2010, appearing in Christopher Nolan's science-fiction thriller "Inception" ...
... and teaming up with Scorsese yet again for "Shutter Island."
He earned another Golden Globe nomination in 2012 for his portrayal of J. Edgar Hoover in Clint Eastwood's "J. Edgar."
DiCaprio took on an unusually villainous role in Quentin Tarantino's Oscar-winning western "Django Unchained," and earned another Golden Globe nomination.
He worked with "Romeo + Juliet" director Baz Luhrmann again for a new adaptation of F. Scott Fitzgerald's "The Great Gatsby."
He starred in Scorsese's "The Wolf of Wall Street," portraying stockbroker Jordan Belfort. He won a Golden Globe and got a fourth Oscar nod. He was also nominated for an Oscar as a producer. After the film, DiCaprio took a break from acting to spend his time "doing good for the environment."
During this acting break, he helped produce "Virunga," a Netflix documentary about the Virunga National Park rangers who risk their lives to protect the world's remaining mountain gorillas. He earned an Emmy nomination for the documentary.
This year, DiCaprio could finally earn his elusive Oscar for his depiction of Hugh Glass in "The Revenant." The film has already earned him a Golden Globe, as well as his first BAFTA win — his fourth nod — and first SAG Award.
He may not have won Hollywood's most prized statue yet, but a survey by Hollywood Reporter found that he makes around $25 million per picture, which puts him in the big leagues with Robert Downey Jr.
In 2015, it was announced that DiCaprio and Scorsese would team up for "The Devil in the White City," an adaptation of the nonfiction book of the same name. DiCaprio will be playing Dr. H. H. Holmes, a serial killer.