"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 the statement.
Hollywood entertainment website TMZ reported that Jolie had filed for full physical custody of all six of their children. TMZ, citing a legal filing, said Jolie "was extremely upset" by Pitt's parenting methods.
The superstar couple were married in 2014 after 10 years together. TMZ reported Jolie cited their separation date as Sept. 15.
Jolie, 41, the estranged daughter of actor Jon Voight, had a bohemian reputation early in her career but more recently has taken on humanitarian causes and was named a special envoy for the U.N. High Commissioner for Refugees. Her six children include sons adopted from Cambodia and Vietnam and a daughter adopted from Ethiopia.
Jolie, who won a best-supporting actress Oscar for "Girl, Interrupted" in 2000, was previously married to actors Jonny Lee Miller and Billy Bob Thornton.
Pitt, 52, one of Hollywood's leading men, was married to actress Jennifer Aniston in 2003 when he and Jolie began filming "Mr. & Mrs. Smith," the story of two professional killers who have unknowingly been assigned to kill each other. There were reports of an affair during that time, but Jolie told Vogue magazine they were only "very, very good friends" until Pitt and Aniston split in 2005.
Jolie and Pitt also starred together the marital drama "By the Sea," a 2015 movie that she wrote and directed.