"We will not resign ourselves to imagining a Middle East without Christians," he said after meeting with Patriarchs from Syria, Irak and Egypt, before calling for "the universal right to lead a dignified life and freely practise one's own faith to be respected."
The Arab Spring uprisings which revolutionised the region have increased tensions between Christians and Muslims.
Francis said he had spoken to the Patriarchs about "those who live in the Middle East, often in small flocks, in environments marked by hostility and conflicts" and "the size of the diaspora, which is notably growing."
He said he was concerned by "the situation of Christians, who suffer in a particularly severe way the consequences of tensions and conflicts in many part of the Middle East."
"Syria, Iraq, Egypt and other areas of the Holy Land sometimes overflow with tears," he said.
The revolts in the region, which saw Islamist parties sweep to power, left many minority Christians scared of persecution from fundamentalist outgrowths and sporadic violence against them has driven some to emigrate.
Francis said he "will not rest while there are still men and women, of any religion, whose dignity is affronted, who are stripped of the basics necessary for survival, whose future is stolen, who are forced to become refugees or displaced people."