In what Church watchers described as a significant toughening of his tone, the pontiff has called on Muslim political, religious and intellectual leaders worldwide to "clearly" speak out in condemnation of those who kill in the name of Islam.
He did so at the risk of offending those in the Muslim world who feel they have done exactly that. And also those who say Western leaders fuel militancy through support for Israel, military interventions in Muslim countries, and mistreatment of believers in their societies.
The pope's appeal came on Sunday evening as he returned from a trip to Turkey.
While in Turkey, the 77-year-old Francis was lectured by President Recep Tayyip Erdogan over the role of what he described as rising anti-Muslim prejudice in Western countries in helping to foment the militancy that has given rise to the Islamic State group in Iraq and Syria.
"People are being labelled as conservative, intolerant and violent just because of their faith," Erdogan said, accusing the media and politicians of reinforcing racist and discriminatory perceptions.
On the eve of the pope's arrival, the Turkish leader, long accused of eroding the secular nature of his country, had delivered an extraordinary speech suggesting "foreigners" loved to exploit and divide Muslims.
"Believe me, they don’t like us. They appear to be our friends, but they want to see us die, see our children die."
Francis's comments were in response to a question about the "Islamaphobia" issue raised by Erdogan.
Responding at length, it was notable that the pope, given his frequent statements on the plight of migrants to Europe, declined to acknowledge any problem with the treatment of Muslims in the West, according to a prominent American Vatican expert.
"He had the opportunity to take the deal and he really didn't" said John Allen, Associate Editor at Crux, the Boston Globe's specialist news service on Catholic issues.
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Allen added: "Other popes, including John Paul II after 9/11 and Benedict XVI, have said similar things but it was the first time that Francis has been this clear in pointing a finger at leaders of the Muslim world and said 'you have to do something'."
NOT LECTURING ANYONE
Francois Bousquet, a Rome-based theologian, said the pope's comments reflected the thinking of his inner circle on the rise of Islamic State, whose militants stand accused of driving Christian and other non-Muslim minorities out of Iraq and Syria.
"If interfaith dialogue is serious, it has to turn into action when inhuman things happen," Bousquet said. He played down predictions of an angry Muslim reaction to Francis's comments along the lines of the furore that erupted when his predecessor Benedict appeared to link Islam to violence.
"The pope is not judging, looking down on or lecturing anyone," Bousquet said. "That is not his tone, it is recalling that we have to live together."
Allen added: "There is always a tension in the Vatican between the diplomatic side and what you could call a more prophetic side who say 'people are getting killed here, and some of them are our people - we can't be soft about this.'"
SOUL OF ISLAM
"There's also a view that there is a struggle for the soul of Islam going on right now and they are trying to figure out how to ensure the right side wins.
"What we are seeing here is Francis coming down on the side of the argument that you have got to almost shame them (moderates) into acting."
Valentino Cottini, the head of the Pontifical Institute for Arab and Islamic Studies, suggested Francis was essentially appealing to ordinary Muslims, in the absence of a religious hierarchy with the kind of influence the Vatican has over its global flock.
"There have already been many condemnations but the issue is who are the opinion makers in the Islamic world," Cottini said. "What type of Islam is driven by the mass media and social networks?" he said.