The estranged couple said in a statement to the magazine, "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," the statement concluded.
Almost a year after they were first linked in the winter of 2011, Barrymore, 41, and Kopelman got engaged. They were married a few months later, in June 2012, when the actress was pregnant with their oldest daughter Olive, now 3. They welcomed a second daughter, Frankie, in November 2013.
Having a solid family unit was important to Barrymore, who had a tumultuous childhood and a roller-coaster relationship with her mother, Jaid.
"Will comes from a good family, he provides a strong family, it's amazing," she told People in 2012. "For people who didn't have the strongest families, or traditional families, if you can create that, you have a second chance. It just makes me so emotional because it's like a miracle."
This was the third marriage for Barrymore. She married bartender Jeremy Thomas in 1994, though they split two months later. Her 2001 marriage to comedian Tom Green lasted less than a year as well.