The actor had suffered a brain aneurysm on February 18 at his home in Los Angeles.
He died in his sleep on Friday at a hospital in Burbank, California, his manager Charles Lago said.
Sizemore became a star with acclaimed appearances in Natural Born Killers and the cult-classic crime thriller Heat.
But serious substance dependency, abuse allegations and multiple run-ins with the law devastated his career, left him homeless and sent him to jail.
As the global MeToo movement wave crested in late 2017, Sizemore was also accused of groping an 11-year-old Utah girl on set in 2003.
He called the allegations "highly disturbing", saying he would never inappropriately touch a child.
Charges were not filed.
Despite the raft of legal trouble, Sizemore had scores of steady film and television credits - though his career never regained its one-time momentum.
Aside from Black Hawk Down and Pearl Harbor, most of his 21st century roles came in low-budget, little-seen productions where he continued to play the gruff, tough guys he became famous for portraying.
"I was a guy who'd come from very little and risen to the top.
"I'd had the multimillion dollar house, the Porsche, the restaurant I partially owned with Robert De Niro," the Detroit-born Sizemore wrote in his 2013 memoir, By Some Miracle I Made It Out of There.
"And now I had absolutely nothing."
The book's title was taken from a line uttered by his character in Saving Private Ryan, a role for which he garnered Oscar buzz.
But he wrote that success turned him into a "spoiled movie star", an "arrogant fool" and eventually "a hope-to-die addict".
He racked up a string of domestic violence arrests.
Sizemore was married once, to actor Maeve Quinlan, and was arrested on suspicion of beating her in 1997.
While the charges were dropped, the couple divorced in 1999.
Sizemore was convicted of abusing ex-girlfriend Heidi Fleiss in 2003, the same year he pleaded no contest and avoided trial in a separate abuse case, and was sentenced to jail.
Many of Sizemore's later-career films had a sci-fi, horror or action bent: In 2022 alone, he starred in movies with such titles as Impuratus, Night Of The Tommyknockers and Vampfather.
But Sizemore still nabbed a few meaty roles, including in the Twin Peaks revival, and guest spots on popular shows like Entourage and Hawaii Five-O.
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