Weinstein's sentencing for sexually assaulting one-time TV production assistant Miriam Haley followed a legal odyssey spanning more than six years.
His 2020 conviction was overturned by New York's highest court, citing testimony from other women whose allegations were not part of the case.
A second jury found Weinstein guilty again at a retrial last year.
Once among the most powerful figures in the entertainment industry, Weinstein was an Oscar-winning producer whose hits included Shakespeare in Love, Pulp Fiction and Chocolat.
But his downfall came quickly after sexual assault allegations in 2017 set off the MeToo movement.
Weinstein, 74, is expected to appeal.
He is now likely to remain behind bars until at least his late 80s.
He has denied raping or sexually assaulting anyone.
Seated in a wheelchair, he was quickly wheeled out of the courtroom after the sentencing, while some of his accusers hugged and brushed away tears.
Weinstein faced up to 25 years in prison for sexually assaulting Haley at his Manhattan apartment in 2006.
He has already served more than six years as his case has cycled again and again through the criminal justice system.
Haley gave her account of the assault at two trials, and addressed the court on Wednesday just before Weinstein was sentenced.
"Having been sexually assaulted by Harvey Weinstein has had a devastating effect on my life and sense of security that may never go away. Making the decision to speak up will have me looking over my shoulder for years to come," Haley said.
"It's a life sentence for me."
"I've been further traumatised in exercising my right to hold him accountable. All of this traces back to his actions," she said, adding that she thought about ending her pursuit of justice many times.
Minutes later, Weinstein apologised in court to those he may have hurt.
"I do have remorse for Miriam Haley's pain but I have to reiterate my innocence," he told the judge.
Judge Curtis Farber said Weinstein was once a king in the movie industry, "but recognition for these achievements will pale in comparison to what you did".
He said Weinstein is now known as "a sexual predator, the literal face of the MeToo movement".
Weinstein was originally sentenced to 23 years in prison after a jury convicted him of assaulting Haley and raping an aspiring actress, Jessica Mann, in 2013.
Tried for a second time last year, he was again convicted of a first-degree criminal sex act for assaulting Haley, who has also gone by the name Mimi Haleyi.
In a messy split verdict, the jury acquitted him of forcibly performing oral sex on another woman, Kaja Sokola, and could not reach a verdict on a rape charge involving Mann.
"I will be proven innocent. That I promise you," Weinstein told The Hollywood Reporter in a jailhouse interview in March.
After another retrial ended in a hung jury in May, Manhattan prosecutors dropped the rape charge rather than pursue a fourth trial after Mann said she could not bear to testify again.
That decision cleared the way for Weinstein's sentencing.
Defence lawyer Jacob Kaplan asked that Weinstein receive a sentence of three more years on top of the six years he has already served, saying a longer sentence would make it more likely that Weinstein dies in prison.
Weinstein is in failing health and has been in the hospital six times since 2025, Kaplan said, while dealing with blood cancer, congestive heart failure and kidney issues.
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