Angelina's lawyer, Robert Offer, confirmed that the star began the proceedings for 'dissolution of marriage' on Monday, saying the 'decision was made for the health of the family'.
In a statement he added: 'She will not be commenting, and asks that the family be given its privacy at this time.'
It is believed the actors first started dating in 2005 on the set of Mr and Mrs Smith, and married in a private ceremony in August 2014.
Brad and Angelina also have six children together: Maddox, 15, Zahara, 11, Shiloh, 10, Pax 12 and twins Knox and Vivienne aged 8.
Maddox, Zahara and Pax were all adopted from orphanages from Cambodia, Ethiopa and Vietnam, while the other three are the couple's biological children.
According to a report by The Sun, Brad and Angelina had been living separate lives for a few months, after having a number of arguments over their children and the future.
A source told The Sun: ‘Angelina is very unhappy with the marriage and is considering splitting from Brad.
‘There have been rumours around the status of the relationship for years, but they are now very much in turmoil and it is hard to see a way out.
‘There have been a constant string of arguments about their future and their children.
The same source adds: ‘They have come through a lot before and somehow managed to keep up appearances but Brad thinks this time is different.'
The pair made their last public appearance at the premiere of By The Sea, the film written and directed by Angelina about an unhappy couple, in November 2015.
Most recently, Angelina, 41, has been focussing on her humanitarian work as a special envoy to the UN, while Brad, 52, has been negotiating a deal to launch a resort in Croatia.