|Harvey Weinstein and Georgina Chapman married in 2007|
British fashion designer Georgina Chapman described her husband's behaviour as "unforgivable" and said "my heart breaks for all the women who have suffered tremendous pain".
It comes amid claims Weinstein raped three women and admitted groping a model in a recording obtained by The New Yorker.
Hollywood stars Gwyneth Paltrow and Angelina Jolie have also accused the movie producer of making unwanted advances towards them.
Weinstein continues to "unequivocally deny" allegations of non-consensual sex against him, and of illegal sexual harassment.
In a statement, his wife told People magazine: "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."
The couple married in 2007 and have two children together - India Pearl, seven, and Dashiell Max Robert, four.
Former US president Barack Obama said he and his wife Michelle were left "disgusted" by the allegations against Weinstein, who has been a major donor to the Democratic Party since the early 1990s.
Michelle Obama pictured with Harvey Weinstein in 2013
Mr Obama added: "Any man who demeans and degrades women in such fashion needs to be condemned and held accountable, regardless of wealth or status."
Paltrow claimed she was propositioned by Weinstein after he hired her to star in Emma when she was 22 years old.
The star told The New York Times that during a meeting in his hotel suite the film producer placed his hands on her and suggested they head to the bedroom for massages.
"I was a kid, I was signed up, I was petrified," she said.
Brad Pitt was said to have confronted Weinstein over the alleged incident with Paltrow
Paltrow said she refused his advances and ended up telling her then-boyfriend Brad Pitt, who confronted him, which resulted in Weinstein warning her not to tell anyone else.
It left her believing "he was going to fire me", she said.
|Jolie said she 'had a bad experience' with Weinstein in her youtg|
Jolie said she "had a bad experience" with Weinstein in her youth, causing her to never work with the producer again and warning others about his conduct.
The claims come as The New Yorker alleges Asia Argento, an Italian actress, told the magazine Weinstein forcibly performed a sex act on her.
She and two other women also allege that Weinstein raped them, The New Yorker claimed.
Jolie said she 'had a bad experience' with Weinstein in her youth
Meanwhile, a police recording has emerged purporting to be of Weinstein trying to persuade an Italian model to enter his hotel room.
The New Yorker published the recording in a story that also featured further allegations against Weinstein, who was fired from the company he founded following claims of sexual harassment.
The recording, said to be made by New York Police Department, apparently features a conversation between the film producer and Ambra Battilana Gutierrez at the entrance to his hotel room.
Gutierrez is heard telling Weinstein clearly she is "not comfortable" with the situation as he tells her repeatedly to come and sit next to him and to go to the bathroom after saying he is going to have a shower.
Towards the end of the recording, Gutierrez asks Weinstein: "Why yesterday you touch my breast?", to which he responds: "Oh, please, I'm sorry, just come on in. I'm used to that. Come on. Please."
Gutierrez responds: "You're used to that?" to which Weinstein says: "Yes, come in."
She then tells him: "No, but I'm not used to that," to which he replies: "I won't do it again, come on, sit here."
Earlier in the recording, Weinstein is heard saying: "I'm telling you right now, get in here.
"I'm going to take a shower. You sit there and have a drink."
When Gutierrez asks if she can stay by the bar, he tells her: "No, you must come here now."
Gutierrez tells him: "Yesterday was kind of aggressive for me. I need to know a person to be touched.
He says: "I won't do a thing. I swear I won't, just sit with me. Don't embarrass me in the hotel, I'm here all the time."
The producer then appears to use language that is increasingly more direct, telling Gutierrez: "If you do this now, you will embarrass me. Now go. Bye. Never call me again. Okay? I'm sorry, nice to have…I promise you I won't do anything."
He adds: "The guy is coming. I will never do another thing to you. Five minutes. Don't ruin your friendship with me for five minutes."
When she says it's "too much" for her, he tells her: "Please, you're making a big scene," before, when she still will not submit, saying: "Okay. Bye. Thank you."
Manhattan District Attorney's office said the recording was arranged by the NYPD in 2015 without its input and as a result its prosecutors were not able to discuss with investigators what was necessary to capture to prove a sex crime.
Chief Assistant DA Karen Friedman-Agnifilo said: "If we could have prosecuted Harvey Weinstein for the conduct that occurred in 2015, we would have.
"While the recording is horrifying to listen to, what emerged from the audio was insufficient to prove a crime under New York law, which requires prosecutors to establish criminal intent.
"This, coupled with other proof issues, meant that there was no choice but to conclude the investigation without criminal charges."
In his latest statement, Weinstein denied "there were never any acts of retaliation against any women for refusing his advances".
The multiple Oscar winner had taken a voluntary leave of absence from the Weinstein Company after the harassment allegations were detailed in The New York Times last week.
The firm he founded with his brother Bob sacked him on Sunday evening after several women claimed he had harassed them.