The Hollywood actress, 41, and art consultant Will, 38, announced the sad news in a joint statement on Saturday (2 April).
Printed in the People, the statement says: "Sadly our family is separating legally, although we do not feel this takes away from us being a family.
"Divorce might make one feel like a failure, but eventually you start to find grace in the idea that life goes on.
"Our children are our universe, and we look forward to living the rest of our lives with them as the first priority."
Drew married third husband Will in June 2012.
They share daughters, Olive, three, and 23-month-old Frankie.
The last time she shared a photo of herself and her husband on social media, it was to celebrate their wedding anniversary last year.
She wrote: "Happy anniversary Mr. Kopelman, cheers to you! I love you and I love our daughters!!!!!!! #threeyears."
Just days ago, Drew had the names of her two daughters tattooed on the inside of her wrist.
She revealed the simple inking to her four million Instagram followers on 1 April (Friday).
In another photo, the ET actress posed alongside the tattoo artist. Sharing this picture, Drew wrote: "Getting a great little lifetime note on my arm."
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