Weinstein, 73, was brought into a Manhattan courtroom in a wheelchair on Wednesday, dressed in a dark suit and navy tie.
He has pleaded not guilty to two counts of first-degree criminal sexual act and one count of third-degree rape.
He could face decades in prison if convicted.
Weinstein's conviction had been a capstone moment for the MeToo movement, which encouraged women to come forward with allegations of sexual misconduct by powerful men.
More than 100 women, including famous actresses, accused Weinstein of misconduct.
The Miramax studio co-founder, once one of Hollywood's most powerful producers, has denied assaulting anyone or having non-consensual sex.
The new trial before state Supreme Court Justice Curtis Farber is expected to last roughly six weeks.
Manhattan District Attorney Alvin Bragg attended the start of the retrial.
"We're hoping that Mr Weinstein is going to get a fair trial this time," Imran Ansari, one of his lawyers, told reporters.
"He wants to clear his name."
A different jury found Weinstein guilty of rape and sexual assault in 2020, and he was sentenced to 23 years in prison.
Prosecutors portrayed Weinstein as a serial predator who promised career advancement in Hollywood to women, only to then coax them into hotel rooms and private apartments where he overpowered and attacked them.
But the state Court of Appeals threw out Weinstein's conviction last April and ordered a new trial.
It said that the trial had been unfair because the original judge let women testify that Weinstein assaulted them even though their accusations were not the basis for criminal charges.
Bragg's office is again accusing Weinstein of sexually assaulting former production assistant Miriam Haley in 2006 and raping aspiring actress Jessica Mann in 2013, charges he was convicted of in the first trial.
For the retrial, prosecutors added a new charge that Weinstein assaulted an unidentified woman in Manhattan in 2006.
Even if he is acquitted, Weinstein will likely spend the rest of his life in prison because he was convicted of sex crimes in California and was sentenced to a 16-year term.
Weinstein has had several health scares while being held in New York City's Rikers Island jail, and in September was rushed to a hospital for emergency heart surgery.
Citing his health, Weinstein's lawyers are seeking a court order to let him stay overnight at Bellevue Hospital in Manhattan for the duration of the trial.
Weinstein's representatives have said he has received inadequate medical care at Rikers.
Lindsay Goldbrum, a lawyer representing the new unidentified victim, called the retrial a pivotal moment in the fight against sexual abuse.
"More than seven years after MeToo, this case will test how far we've advanced in our collective understanding of sexual assault, power dynamics, and what it means to be a survivor," Goldbrum said in a statement.
Weinstein's film studio filed for bankruptcy in March 2018, five months after the original sexual misconduct accusations became widely publicised.
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