In a new statement, the Hollywood actor has said he feels "saddened" by his and Angelina's break-up, adding that his main priority is their six children.
"I am very saddened by this, but what matters most now is the well-being of our kids," he said in the statement, released to America's People magazine.
He continued: "I kindly ask the press to give them the space they deserve during this challenging time."
After being together for a decade, Brad and Angelina finally tied-the-knot in August 2014 on their private estate in France. The couple had become engaged in 2012, however they insisted they would only wed once same-sex marriage was legal in California.
Brad and Ange - Brangelina as they are famously known - have six children together; sons Maddox, Pax and Knox, and daughters Zahara, Shiloh and Vivienne.
News of their split has shocked the world, with celebrities speaking out in the wake.
Angelina's lawyer previously stated that it was her decision to end her marriage with Brad. In a brief statement, her attorney said: "This decision was made for the health of the family. She will not be commenting, and asks that the family be given its privacy at this time."
This will be Brad's second divorce, as he was previously married to Friends star Jennifer Aniston. Brad, now 52, famously began dating Angelina back in 2004 after filming Mr and Mrs Smith together.
Although he was married to Jennifer during filming, he later said he "fell in love" with Angelina on set.
Angelina, 41, has been divorced twice, following marriages to actors Johnny Lee Miller and Billy Bob Thornton.