Islamists stormed Qaraqosh overnight forcing Kurdish troops to leave and Christians to flee to safety.
Last month ISIS issued an ultimatum to Christians in other parts of Iraq to convert to Islam, pay a tax or face death.
The Holy Father's spokesman Fr. Federico Lombardi has released a statement: "The Holy Father is following with deep concern the dramatic news reports coming from northern Iraq, which involve defenseless populations.
"Christian communities are particularly affected: a people fleeing from their villages because of the violence that rages in these days, wreaking havoc on the entire region.
"In light of these terrible developments, the Holy Father renews his spiritual closeness to all those who are suffering through this painful trial, and makes the impassioned appeals of the local bishops his own, asking together with them in behalf of their sorely tried communities, that the whole Church and all the faithful raise up with one voice a ceaseless prayer, imploring the Holy Spirit to send the gift of peace.
"His Holiness urgently calls on the international community to protect all those affected or threatened by the violence, and to guarantee all necessary assistance – especially the most urgently needed aid – to the great multitude of people who have been driven from their homes, whose fate depends entirely on the solidarity of others.
"The Pope also appeals to the conscience of all people, and to each and every believer he repeats: 'May the God of peace create in all an authentic desire for dialogue and reconciliation. Violence is not conquered with violence. Violence is conquered with peace! Let us pray in silence, asking for peace; everyone, in silence.... Mary Queen of peace, pray for us'."
Many children of the Christian families forced to flee their homes are said to be dying from thirst.
Local Archbishop Yousif Thomas Mirkis has told Premier's News Hour they've had to evacuate on foot and the heat is becoming unbearable.
He said: "There are more than 100,000 Christians who are now on the road under the sun.
"The heat is now 45°Celsius.
"Many children are now dying from thirst and the heat.
"Politicians must hear our voice and the voice of the poorest.
"Politicians both inside and outside the must hear the cry and the suffering of the poorest in the population."
Christian Solidarity Worldwide Special Ambassador Stuart Windsor told Premier: "We're deeply saddened by this news.
"There seems to be no end to this. Christians have fled the areas and the fact another has fallen is really so sad.
"We're urging Christians everywhere to pray for Iraq and we pray that this cleansing will come to an end and that we can see the international community do something about this terrible situation."
Listen to more from Archbishop Yousif Thomas Mirkis here: