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.
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."
News of the split is sure to put a dampener on Lopez's upcoming birthday - she turns 42 on July 24.
It is American Idol host Lopez's third failed marriage. Anthony was previously married to former Miss Universe, Dayanara Torres, mother of his two sons Cristin, 10, and Ryan, seven.