British fashion designer Georgina Chapman said her "heart breaks for all the women who have suffered tremendous pain", as Hollywood stars Gwyneth Paltrow and Angelina Jolie joined a growing list of Weinstein's alleged victims.
It comes as Weinstein reportedly flew to Europe by private jet to check into rehab to undergo therapy for sex addiction and "other behavioral issues".
Ms Chapman, 41, broke her six-day silence by telling People magazine she has left the film mogul, whom she married in 2007.
After Weinstein earlier claimed that his wife was standing by him, she said in a statement: "My heart breaks for all the women who have suffered tremendous pain because of these unforgivable actions. I have chosen to leave my husband.
"Caring for my young children is my first priority and I ask the media for privacy at this time."
Ms Chapman made the announcement as the 65-year-old Hollywood producer was accused of rape by three other women in an explosive expose in the New Yorker magazine.
The allegations marked a shocking escalation of a scandal that has engulfed Hollywood.
Both Paltrow and Jolie described how the producer, who was instrumental in launching Paltrow's career, made unwanted advances toward them in hotel rooms.
In the same article in the New York Times, five other women went on the record to allege sexual assualt or harassment at the hands of Weinstein.
He has vehemently denied the claims and said all his sexual relations were consensual.
Weinstein also denied claims by the actresses Rosanna Arquette and Mira Sorvino that he damaged their careers after they rejected his unwanted advances.
The producer initially apologised for causing anyone pain last week and said he was seeking therapy.
On Tuesday night, Weinstein flew to Europe to enter a rehab centre for sex addiction other behavioral issues, TMZ reported.
"He wants to come back with fresh, new ideas," the celebrity news website quoted a source as saying.
'I was petrified': Paltrow describes encounter
Paltrow was 22 when Weinstein hired her for her breakthrough lead role in an adaptation of Jane Austen's Emma.
Before filming she was asked to visit his suite at the Peninsula Beverly Hills hotel for a work meeting, Paltrow told the New York Times.
She said Weinstein then attempted to encourage her into his bedroom for massages. The actress told the New York Times: "I was a kid, I was signed up, I was petrified. I thought you were my Uncle Harvey."
Paltrow refused and confided in her then boyfriend Brad Pitt who later confronted Weinstein and told him never to touch her again.
The actress said Weinstein yelled at her for telling Pitt and she thought she would be fired. She said: "He screamed at me for a long time. It was brutal. I was expected to keep the secret."
She added: "We’re at a point in time when women need to send a clear message that this is over. This way of treating women ends now."
Jolie tells of 'bad experience in my youth'
Paltrow's account was echoed by Jolie, who said Weinstein made unwanted advances to her in a hotel room during the release of Playing by Heart in the late 1990s. She rejected him.
Jolie told the New York Times: "I had a bad experience with Harvey Weinstein in my youth, and as a result, chose never to work with him again and warn others when they did.
"This behaviour towards women in any field, any country is unacceptable.”
The New Yorker also published an audio tape of a conversation between Weinstein and an Italian model from 2015, in which he can be heard apparently confessing to sexual assault.
Weinstein championed the careers of a host of A-list stars, and counted the Clintons and Obamas as friends.
Hilary Clinton said she was "shocked and appalled" by the allegations, in her first remarks since reports emerged.
She said: "The behaviour described by women coming forward cannot be tolerated. Their courage and the support of others is critical in helping stop this kind of behaviour."
Obamas are 'disgusted' by Weinstein claims
Barack Obama also broke his silence on the scandal, saying he and his wife Michelle were "disgusted by the recent reports".
"Any man who demeans and degrades women in such fashion needs to be condemned and held accountable, regardless of wealth and status.
"We should celebrate the courage of women who have come forward to tell these painful stories. And we all need to build a culture - including by empowering our girls and teaching our boys decency and respect - so we can make such behaviour less prevalent in the future."
Amid claims Weinstein's behaviour had been an open secret in Hollywood, George Clooney, who got his first big movie break from the producer, said: "I've never seen any of this behaviour - ever.
"If you're asking if I knew that someone who was very powerful had a tendency to hit on young, beautiful women, sure."
But he had "no idea" that "women were threatened and victimised".
Ben Affleck, who also got his first big break from Weinstein, said he felt "sick" after reading the allegations.
Colin Firth, who starred in the Oscar-winning and Weinstein-produced King's Speech, said he was reading the reports with a feeling of nausea.
"He was a powerful and frightening man to stand up to. It must have been terrifying for these women to step up and call him out," he said in a statement to the Guardian. "And horrifying to be subjected to that kind of harassment. I applaud their courage,."
Arquette told Weinstein: I'll never be that girl
In an article in the New Yorker, Asia Argento, an Italian actress best known for her role in the action film xXx, and a former aspiring actress named Lucia Evans went on the record to allege Weinstein had raped them.
A third woman who also said Weinstein raped her declined to be named.
In both articles, Rosanna Arquette claimed that in the early 1990s she went to pick up a script at the Beverly Hills Hotel, arriving at Weinstein's room to find him in a bathrobe and asking for a massage.
She claimed he then tried to forcibly initiate a sexual encounter and, when she refused, named another actress who had advanced her career that way. Arquette said she told him: "I’ll never be that girl."
The article was written by Ronan Farrow, the son of Mia Farrow and Woody Allen, who said it was the result of a 10-month investigation.
Farrow said he spoke to a total of 13 women who claimed Weinstein sexually harassed or assaulted them between 1990 and 2015.
Some of those incidents overlapped with eight allegations of sexual harassment reported by The New York Times last week, all of which resulted in financial settlements.
The New Yorker published an audio tape of a conversation between Weinstein and Italian model Ambra Battilana Gutierrez, in 2015.
Weinstein 'caught on tape' in police sting
She had gone to New York police following a previous encounter in Weinstein's office when she said he lunged at her, groping her breasts, and tried to put a hand up her skirt.
Gutierrez was fitted with a wire by police in a sting operation. On the tape he could be heard encouraging her into his room as she repeatedly said "I don't want to".
She asked him why he had touched her breast the previous evening. Weinstein said "I’m used to that. Come on. Please." He added: "Don't ruin your friendship with me for five minutes."
Miss Gutierrez, a former Miss Italy finalist, was previously invited to one of former Italian Prime Minister Silvio Berlusconi's infamous "bunga-bunga" parties when she was 18.
The model said she was shocked by the event and demanded to be taken home.
Argento said she was 21 when she invited to a studio party at the Hôtel du Cap-Eden-Roc, on the French Riviera in 1997.
She said Weinstein was the only person there and changed into a bathrobe before asking her to give him a massage. She claimed he forced himself on her and she was "terrified".
Mira Sorvino told the New Yorker that Weinstein came to her hotel room and she got him to leave by saying her new boyfriend was arriving.
On the effect on her career she said: "I definitely felt iced out and that my rejection of Harvey had something to do with it.”
In a statement to the New Yorker, a spokeswoman for Weinstein said: "Any allegations of non-consensual sex are unequivocally denied by Mr Weinstein. Mr Weinstein believes that all of these relationships were consensual.
"Mr Weinstein has further confirmed that there were never any acts of retaliation against any women for refusing his advances."
The statement added: "Mr Weinstein has begun counseling, has listened to the community and is pursuing a better path. Mr Weinstein is hoping that, if he makes enough progress, he will be given a second chance.”
Lindsay Lohan 'feels very bad' for Weinstein
Lindsay Lohan is one of the few celebrities to defend Weinstein. In a video post on Instagram, the star asked his wife to stand by him, adding that he had "never harassed or assaulted her".
Filming herself from Dubai, Ms Lohan said: "I feel very bad for Harvey Weinstein right now, I don't think it's right what's going on.
"I think Georgina needs to take a stand and be there for her husband."
She added: "He's never harmed me or did anything to me — we've done several movies together. I think everyone needs to stop — I think it's wrong. So stand up."
'He asked me to watch him perform sex act': Screenwriter Louisette Geiss is latest accuser
A former actress and screenwriter alleged Harvey Weinstein appeared in an open bathrobe with no clothes on during a meeting at the 2008 Sundance Film Festival.
Louisette Geiss said the film mogul asked several times that she watch him perform a sex act during the 2008 encounter.
Geiss made the allegations on Tuesday during a news conference with attorney Gloria Allred, who invited Weinstein to meet with his alleged victims in a mediation or arbitration process.
Geiss said in a statement that she is coming forward to help give voice to other alleged victims of sexual harassment.
She said her experience with Weinstein led to her departure from the entertainment industry. She now works in property.
Weinstein Co. 'shocked' by allegations
The Weinstein Co of Representatives issued a statement on Tuesday night, saying the alleged actions were "antithetical to human decency". "The Weinstein Company's Board of Representatives - Bob Weinstein, Lance Maerov, Richard Koenigsberg and Tarak Ben Ammar - are shocked and dismayed by the recently emerged allegations of extreme sexual misconduct and sexual assault by Harvey Weinstein.
"These alleged actions are antithetical to human decency. These allegations come as an utter surprise to the Board. Any suggestion that the Board had knowledge of this conduct is false.
"We are committed to assisting with our full energies in all criminal or other investigations of these alleged acts, while pursuing justice for the victims and a full and independent investigation of our own."