The spiritual leader of the world's estimated one billion Catholics held a rite lasting about one-and-a-half hours at St. Peter Basilica on Sunday.
"The first 'genocide' of the 20th century struck Armenians," the Pope said.
Armenian President Serzh Sargsyan; Catholicos Karekin II, the current Catholicos of All Armenians and also the supreme head of the Armenian Apostolic Church, and Aram I Keshishian, the head of the Catholicosate of the Great House of Cilicia, also attended the rite.
The 1915 events took place during World War I when a portion of the Armenian population living in the Ottoman Empire sided with the invading Russians and revolted.
The Ottoman Empire relocated Armenians in eastern Anatolia following the revolts and there were some Armenian casualties during the relocation process.
Armenia has demanded an apology and compensation, while Turkey has officially refuted Armenian allegations over the incidents saying that, although Armenians died during the relocations, many Turks also lost their lives in attacks carried out by Armenian gangs in Anatolia.
The Turkish government has repeatedly called on historians to study Ottoman archives pertaining to the era in order to uncover what actually happened between the Ottoman government and its Armenian citizens.
The debate on "genocide" and the differing opinions between the present day Turkish government and the Armenian diaspora, along with the current administration in Yerevan, still generates political tension between Turks and Armenians.
Turkey's official position against allegations of "genocide" is that it acknowledges the past experiences were a great tragedy and that both parties suffered heavy casualties, including hundreds of Muslim Turks.
Turkey agrees that there were certainly Armenian casualties during World War I, but that it is impossible to define these incidents as "genocide".