Speaking at Sunday's Mass in the Armenian Catholic rite at Peter's Basilica, he said that "our human family has lived through three massive and unprecedented tragedies."
"The first, which is widely considered 'the first genocide of the 20th Century', struck your own Armenian people," the Pontiff added.
According to him, the other two genocides of the 20th century were "perpetrated by Nazism and Stalinism."
Historians say that up to 1.5 million Armenians were killed by Ottoman forces between 1915 and 1917.
Turkey summoned the Vatican ambassador over the Pope's "genocide" remark, AP reports. Prior to that, Turkey's embassy to the Holy See canceled a planned news conference for Sunday, presumably after learning that the pope would utter the word "genocide" over its objections.
Ankara is yet to make an official statement on Pope Francis' genocide comments.
Turkey vehemently rejects the claims, arguing that the number of deaths was much smaller.
Ankara said that many of those killed allegedly died in clashes during World War I and that ethnic Turks also suffered in the conflict.
Argentina, Belgium, Canada, France, Italy, Russia and Uruguay already recognize the Armenian genocide.