Weinstein, 74, was a top Hollywood film producer until sexual misconduct allegations against him led to his downfall and fuelled a wider social movement that encouraged women to come forward with accounts of sexual abuse by powerful men.
He has pleaded not guilty to one count of third-degree rape and has denied assaulting anyone or having non-consensual sex.
Prosecutor Candace White told jurors that Weinstein raped aspiring actress Jessica Mann in a Manhattan hotel room in 2013 while Mann resisted and repeatedly said "No".
"This case will come down to power, to control and to manipulation," White said, accusing Weinstein of preying upon "fragile and sheltered" young women with dreams of Hollywood stardom.
Defence lawyer Jacob Kaplan accused Mann of fabricating the rape allegation after regretting that her romance with Weinstein failed to advance her film career.
He told jurors that emails will show Mann was a "strong and capable" woman whose relationship with Weinstein was consensual.
Testimony in the case was set to begin on Tuesday afternoon.
Weinstein's prior trial conviction for raping Mann was overturned on appeal, and a jury in a second trial was unable to reach a verdict on that charge.
The latest trial before Justice Curtis Farber began with jury selection last week in Manhattan state court and is expected to last about a month.
At his first trial in New York in 2020, Weinstein was convicted of raping Mann in 2013 and assaulting one-time production assistant Miriam Haley in 2006 but the state's highest court overturned the conviction and Weinstein's 23-year prison sentence after concluding he did not get a fair trial.
A Manhattan jury then convicted Weinstein of sexually abusing Haley at a trial in June 2025 but found him not guilty of assaulting former model Kaja Sokola.
The jury deadlocked on the third-degree rape charge accusing Weinstein of assaulting Mann, leading Farber to declare a mistrial on that count.
Weinstein was also convicted of rape in California in 2022, and is serving a 16-year prison sentence.
He is appealing that conviction and sentence.
Weinstein will face up to 25 years in prison when he is sentenced for abusing Haley.
