The couple, known collectively as Brangelina, married in 2014 after 10 years together.
Robert Offer, Jolie’s lawyer, said she has filed for the dissolution of the marriage “for the health of the family”.
Jolie cited irreconcilable differences in legal documents filed on Monday, the celebrity news website TMZ said.
They first met when they played married spies in Mr And Mrs Smith, when Pitt was still married to Friends star Jennifer Aniston.
Jolie is asking for physical custody of the couple’s six children - Maddox, Pax, Zahara, Shiloh, and twins Knox and Vivienne, the website claimed.
The Maleficent star is apparently being represented by divorce lawyer Laura Wasser, who helped in her divorce from Billy Bob Thornton and is representing Johnny Depp in his divorce from Amber Heard.
The couple married in private at their chateau in France in 2014.
They had waited for gay marriage to become legal, with Pitt telling Esquire magazine in 2006: “Angie and I will consider tying the knot when everyone else in the country who wants to be married is legally able to.”
Their ceremony included all their children, including adopted offspring Maddox, Pax and Zahara and their daughter Shiloh and twins Knox and Vivienne.
Jolie’s Atelier Versace gown featured dozens of designs from her children’s drawings sewn into the dress and veil and the children served as ring bearers and threw flower petals.
Jolie was previously married to Thornton and British actor Jonny Lee Miller.
Since Mr And Mrs Smith, the couple have appeared on screen together in By The Sea, a film written and directed by Jolie and produced by Pitt, in which they played a glamorous couple whose marriage is in crisis.
Before they began filming, Jolie told the Radio Times: “It feels a little daunting. We haven’t worked together for 10 years. But all of the reasons why people say we should be scared of it, we feel that’s exactly why we have to do this - because we can. So we’re going to go boldly.”
She added: “He’s a pretty strong actor. It’s going to be interesting. He’s a really great artist, such an interesting artist, and of course he’s the man I love, so I think we’re going to have a great time.”
In May 2013 Jolie had a preventative double mastectomy after tests showed that she carries the BRCA1 cancer gene, and she later told the American show Today: “I knew through the surgeries that he was on my side and that this wasn’t something where I was going to feel less of a woman because my husband wasn’t going to let that happen.
“To face these issues together and speak about them and talk about what it is to be human, I think can be a beautiful thing.”
Rise and fall of Branjelina
Angelina Jolie and Brad Pitt met on the set of action comedy film Mr & Mrs Smith, while Pitt was still married to Friends star Jennifer Aniston. Jolie had recently divorced Billy Bob Thornton.
Both movie stars denied rumours that they had begun an affair during filming, insisting their romance began later.
• January 2005:
Pitt and Aniston announced their decision to split after nearly five years of marriage.
• March 2005:
Aniston then filed for divorce, citing “irreconcilable differences”.
• April 2005:
Pitt, Jolie and her adopted son Maddox were pictured holidaying together in Kenya, fuelling rumours of a relationship.
• July 2005:
Pitt and Jolie posed for a photo shoot entitled “Domestic Bliss”, but did not confirm their relationship officially. Later that month, Jolie adopted daughter Zahara Marley from an orphanage in Ethiopia.
• October 2005:
Pitt and Aniston finalised their divorce.
• January 2006:
Jolie confirmed she was pregnant with her first child with Pitt. Her children’s surnames were changed to Jolie-Pitt and her film star partner legally adopted Maddox and Zahara.
• May 2006
The couple welcomed their first biological child, daughter Shiloh Nouvel Jolie-Pitt.
• October 2006:
Pitt told Esquire magazine that he and Jolie would only marry “when everyone else in the country who wants to be married is legally able”, backing same-sex marriage. Pitt reaffirmed this in 2011, when New York passed marriage equality legislation.
• March 2007:
Jolie adopted three-year-old Pax from an orphanage in Vietnam.
• July 2008:
Jolie gave birth to twins - a son Knox Leon and a daughter Vivienne Marcheline - completing their family.
• July 2010:
The couple won a privacy case against the News of the World over false allegations that they were separating.
• December 2011:
Jolie revealed to Christiane Amanpour that the couple’s six children were keen for her to get married. She said: “We’ve explained to them that our commitment when we decided to start a family was the greatest commitment you could possibly have. Once you have six children, you’re committed.”
• January 2012:
Pitt indicated he would be open to marrying, telling The Hollywood Reporter: “It seems to mean more and more to our kids. We made this declaration some time ago that we weren’t going to do it till everyone can. But I don’t think we’ll be able to hold out. It means so much to my kids, and they ask a lot. And it means something to me, too, to make that kind of commitment.”
• February 2013:
Jolie underwent a double mastectomy after discovering that she carries a genetic mutation dramatically increasing her chances of cancer. She later had her ovaries removed.
• August 2014:
The couple wed at their estate in the south of France in a private ceremony. Jolie wore a dress covered in drawings by their six children.
• November 2015:
Brangelina made their final official public appearance at the premiere of their movie By the Sea, which flopped. It told the story of a couple - played by Pitt and Jolie - as they tried to repair their troubled marriage.
She told The Telegraph: “Brad and I have our issues, but if the characters were even remotely close to our problems we couldn’t have made the film.
“To be clear: we have fights and problems like any other couple. We have days when we drive each other absolutely mad and want space, but the problems in the movie aren’t our specific problems.”
• September 2016:
A lawyer for Jolie confirmed she had filed for divorce.