The actress/singer wed Anthony in June 2004 and they welcomed twins Max and Emme in February, 2008 - the same year they renewed their vows.
They reaffirmed their love for one another once more last year (10) to mark their sixth anniversary on 5 June.
A statement issued to UsMagazine.com reads: "We have decided to end our marriage. This was a very difficult decision. We have come to amicable conclusion on all matters.
"It is a painful time for all involved, and we appreciate the respect of our privacy at this time."
Anthony was noticeably absent from Lopez's side when she attended the BAFTA Brits To Watch event in Los Angeles last week (09Jul11) - instead, she took her mother Guadalupe to meet royal couple Prince William and Catherine, Duchess of Cambridge.
News of the split is sure to put a dampener on Lopez's upcoming birthday - she turns 42 on 24 July (11).
It is American Idol host Lopez's third failed marriage. She was previously married to Ojani Noa and dancer Cris Judd.
Anthony's ex-wife is former Miss Universe, Dayanara Torres, the mother of his two sons Cristin, 10, and Ryan, seven.