The actors are said to have separated "amicably" after 18 years of marriage.
When website TMZ printed the legal documents of their divorce, the pair confirmed the split.
Official papers cite "irreconcilable differences" as the reason for ending their marriage of nearly two decades, with Melanie, 56, asking for custody of their only child, 17-year-old daughter Stella.
Their joint statement reads: "We have thoughtfully and consensually decided to finalise our almost twenty years marriage in a loving and friendly manner honouring and respecting each other, our family and friends and the beautiful time we have spent together - Melanie & Antonio."
Shrek star Antonio and Working Girl's Melanie first met on the set of 1995 romantic comedy Two Much.
This will be Melanie's 4th divorce after two marriages to Miami Vice star Don Johnson and one to actor Steven Bauer.
The mother-of-three has a 23-year-old daughter, Dakota, with ex-husband Don, and a 27-year-old son Alexander with Steven. Dakota is also an actress and the star of forthcoming film, Fifty Shades Of Grey.
It's 53-year-old Antonio's second divorce, after separating from his first wife Ana Leza in 1995.
Are you sad to hear of Antonio Banderas and Melanie Griffith's divorce? Tell us below!
See the other break-ups that have rocked the world of celebrity in 2014:
Copyright: WENN Apega
Got an iPad or iPhone? Reveal Mag is specially designed to fit!