Reflecting on her acting and producing career, the Legally Blonde actress, 49, said she is "starting to relax into the idea that I'm enough".
"Those at the beginning of my career were incredibly encouraging, but also gave me a lot of real-world advice about how to behave, how to carry myself, what not to do: not to move to Los Angeles," she told Harper's Bazaar UK.
"They said, 'stay in Nashville, be a child for as long as you possibly can'. I was really friendly and bubbly and smiley. People thought I was faking it.
"The perception of being from the South was that I didn't belong to the coastal-elite communities.
"I wasn't part of the art world, or the cool-kid club. It was a culture clash. I didn't understand the sharp elbows and competitive nature of what I did."
The actress, who was born in Louisiana, is known for her roles in Cruel Intentions, American Psycho and Walk The Line which won her an Academy Award for best actress.
Witherspoon was a producer on thriller Gone Girl and adventure drama Wild, which also earned her an Oscar nomination, and she is producing a Legally Blonde prequel series through her media company Hello Sunshine.
"I was probably successful because I had so much anxiety - they go hand in hand," she said.
"I had pressured myself to extreme levels to show up at work in a perfect way.
"We all now know - perfect is not attainable. It's not sustainable.
"I stressed myself out in service of my job, and it got me really, really far.
"I'm rewarded for my anxiety and perfectionism, but I'm getting older and am starting to relax into the idea that I'm enough.
"I mean, I've had an abundance of good fortune, great work opportunities and worked with some of the greatest people on earth."
In 2016 Witherspoon co-founded Hello Sunshine, now part of Candle Media, which aims "to shine a light on where women are now and help them chart a new path forward", according to its website.
"I advocate for storytelling that is inclusive and more reflective of the entire female experience, because it's been shrouded for hundreds of years," she said.
Her company also produced Apple TV drama The Morning Show, which has won three Emmys and stars Witherspoon and Jennifer Aniston as co-anchors of a news program.
Reflecting on her 50th birthday next year, Witherspoon said she wasn't worried about the milestone.
"I like getting older. I think it's great to be wiser and understand your place in a business.
"I've worked really hard to get to that place ... I feel like I'm living my purpose, for sure. I love my job. I love my fans. I'm the captain of my own destiny."
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