TMZ, the US showbusiness website, claimed Jolie has filed papers citing “irreconcilable differences”.
A legal representative for the actress confirmed she has filed papers to dissolve the marriage.
“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,” attorney Robert Offer said in a statement.
The couple have been together since 2005, and married in 2012, and have six children: Maddox, Pax, Zahara, Shiloh, and twins Knox and Vivienne.
TMZ claimed Jolie has requested physical custody of the children and that September 15, 2016 was the date of separation. Sources said there was no third party involved, but that issues arose over parenting.