Griffith files for Banderas divorce
For years they were among Hollywood's hottest couples, with Antonio publicly supporting his wife's treatments for addiction and both supporting charitable causes.
Melanie has filed for divorce in Los Angeles, citing irreconcilable differences for the split.
The actors were married in May 1996 and have a 17-year-old daughter together.
Melanie, 56, is seeking support from her spouse but is willing to pay her own attorney fees, her filing shows.
The actress, who has a tattoo of Antonio's name in a heart on her right shoulder, signed the divorce petition on May 30 but did not specify the date of their separation.
The pair first worked together on the set of the 1995 romantic comedy Two Much and the 53-year-old actor directed his wife in the 1999 film Crazy In Alabama.
In 2011, the couple hosted a fundraiser for President Barack Obama at their Los Angeles home.
Melanie has been married four times, including twice to actor Don Johnson. Antonio has one previous marriage.
He has in recent years served as the voice of the animated character Puss in Boots in the Shrek films and starred in Pedro Almodovar's two most recent films, The Skin I Live In and I'm So Excited!
Melanie was nominated for an Oscar for her performance in the 1998 film Working Girl.
She has recently turned to television work, guest-starring in Hawaii Five-0, 'Hot In Cleveland and Raising Hope. In 2003, she won praise for her role in the Broadway revival of Chicago.