The couple released a joint statement Wednesday reading, "We are not together anymore. It's very difficult and very personal, and we hope everyone can respect our privacy."
The two had been photographed only last week at the restaurant Il Gatto Nero near Clooney's home on Italy's Lake Como, according to the British newspaper the Daily Mail.
"I am a firm believer in marriage, in the future I will be married, but for the time being I am happy as I am," Canalis, 32, told Chi, an Italian publication that was translated by Us Magazine. "I don't need anything to confirm how happy I am."
The Oscar-winning actor, director and producer, 50, who was twice chosen "Sexiest Man Alive" by People magazine, has frequently discussed his aversion to marriage. He was married once, to actress Talia Balsam, from December 1989 to 1993.
Clooney stars in the upcoming "The Ides of March," which he also directed, and "The Descendants." He is filming director Alfonso Cuarón's "Gravity," with Sandra Bullock.