Clooney, 52, is currently in Italy filming a movie while Keibler is in LA working on her new TV show.
The couple had grown apart in recent months and decided to call it quits instead of opting for a long distance relationship, TMZ reported.
"Both sides realized there is no way to have a relationship when you don't see each other. He was very respectful, adult about the situation... He reminded Stacey that they were friends before they dated and wants to be friends after," a source told the website.
After his marriage with Balsam broke down in 1993, Clooney vowed never to marry or have children.