Witherspoon, who is in New York to promote her film A Wrinkle in Time with the TV icon, said it was only after the wave of #MeToo stories that she and other actors realised how endemic the problem was.
She met with other women in Los Angeles and became one of the most active and outspoken members of the #TimesUp movement to end sexual harassment and discrimination at work.
"It started out in October," she said. "Forty women in a room just talking about this is a problem and how are we going to deal with it, because enough is enough, and time's up, we are no longer going to be harassed, we are not longer going to be mistreated or discriminated against or paid less money, we are going to build opportunities for each other."
The Hollywood star, who first revealed her own #MeToo story last October, said at the time that she felt guilt at not speaking out sooner. "I have my own experiences that have come back to me very vividly and I find it really hard to sleep, hard to think, hard to communicate a lot of the feelings that I've been having about anxiety, honest, the guilt for not speaking up earlier.
"[I feel] true disgust at the director who assaulted me when I was 16 years old and anger at the agents and the producers who made me feel that silence was a condition of my employment. And I wish that I could tell you that was an isolated incident in my career, but sadly it wasn't. I've had multiple experiences of harassment and sexual assault and I don't speak about them very often.
"But after hearing all the stories these past few days and hearing these brave women speak up tonight about things that we're kind of told to sweep under the rug and not to talk about, it's made me want to speak up and speak up loudly because I actually felt less alone this week than I have ever felt in my entire career."
In January, she confessed that she felt driven to keep talking about her experience, despite how hard it was. "There's moments that you have to evaluate whether silence is going to be your only option and in certain times that was our only option, but now is not that time," she told Oprah.
As Witherspoon encouraged the women in the room to think about how they could help the woman next to them, her fellow panellist Danai Gurira told her story of seeing her own struggles reflected in women she has now met across the world.
"I'm amazed at how people talk, amazed to sit in Liberia and hear women and girls who had gone through things I couldn't begin to imagine ... and they all wanted to be heard," said the Black Panther actor, who rose to fame in cult series The Walking Dead.
"Almost all of them said to me, no one had ever asked what had happened to them, what they'd gone through or what they wanted next."
In tears, the 40-year-old Zimbabwean-American added: "I had done a rent party, and a friend said he would match whatever I made and that would help me pay my rent. Now, I'm in a different position."
She said she had realised while promoting the hit movie, in which she plays warrior Okoye, that people still cannot picture women in certain roles in real life.
"It is astounding that we're not there yet, but we're not," she added. "We so rarely see such a representation, almost never, people have said to me. I've heard about boys saying at the theatre, I didn't know women could be generals."
Foreign Minister Julie Bishop also appeared at the event, telling the audience that "no nation can reach its potential unless it engages the skills, talents and energy of the half of the population that's female."
She said this would "drive economic growth, strengthen communities and help achieve gender parity, equality ... that's what governments around the world must strive for."
"As Australia's first Foreign Minister, I've placed gender equality and goals at heart of Australia's foreign policy," she said.
"Today we must commit anew to this most important and critical of tasks."