"I started producing on Monster, and it just happened that I felt the need to protect a first-time director, who was really taking a huge risk. The character was very unusual," she said of real-life serial killer prostitute Aileen Wuornos, who was executed in 2002 for killing seven male clients.
"And initially when we went in to get our financing, it became very clear to me that there was this need for me to step in. Because I think the financiers actually thought they were basically paying for a hot lesbian movie with me and Christina Ricci."
The 44-year-old said she knew they were going to "come up against things" — and she was right, including when she started putting on weight for the role.
"There were a lot of fights. As soon as I started gaining weight, I had one of the financiers call me up. Actually, his wife saw me, and she was like, 'Did you see Charlize? Have you seen what she looks like?'"
The stunning South African famously looked almost unrecognizable in the Oscar-winning role, for which she shaved her eyebrows, wore prosthetic teeth and gained 30lbs.
"And I got that call, like, 'What's going on with that?' This is back in the day when it took, like, three weeks for dailies to make it back here, and I got a call at 3AM from the guy," she recalled.
"He was like, 'What are you doing? You never smiled. You look so angry, you look horrible.'"
The resistance, she said, went on until the very last day; no distributor would touch the film, and it wasn't until the day she and Jenkins were about to sign a straight-to-video deal with Blockbuster, that they got an 11th hour call from distributor Bob Berney.
Besides its numerous awards, the film went on to almost octuple its meager $8million budget, taking more than $60million at the box office.
Elsewhere in the interview, Charlize compared dealing with difficult directors to dating a new man.
She claimed that most directors appreciate honesty, and have a thick enough skin to handle direct criticism.
"And then you have other directors... You can't use the same recipe for every one of these people," she said. "I have definitely found with some directors, sometimes it's better not to hammer it. If you just take a step back and let it play out a little bit, they almost get there on their own, without you having to be like, 'This is never going to f--king work'."
"It's like every time you're dating somebody new, and you have to kind of treat it that way."
While discussing the impact Netflix has had on the industry, Charlize couldn't help having a good-natured dig at her 1996 "That Thing You Do" co-star, Tom Hanks.
"I remember so vividly, 25 years ago, working with Tom Hanks, and he wrote in my script, 'Promise me you will never do television,'" she recalled. "Isn't that unbelievable? And look at him now. He can't stop making television."
"I feel like a lot of these places are shaking us and waking us up to how we need to bring back a little bit more bravery," she added. "We need to push the envelope. We need to do scary things because when you make television, those [risks] are the things that are really encouraged."