Following in the footsteps of Pope Benedict XVI who visited Turkey in 2006, Francis prayed alongside the Grand Mufti of Istanbul, Rahmi Yaran, who had his palms turned toward the sky in a Muslim prayer, inside the 17th-century Sultan Ahmet mosque.
"May God accept it," Yaran told the pope, at the end of the prayer that aims to shows respect for Islam and encourage stronger ties between the two faiths.
Lombardi, who was behind the pope said Francis told the Mufti two times that we "adore" God and not just praise and glorify him.
Earlier, Francis nodded, smiled and looked up in awe as Yaran gave him a tour of the mosque which is famed for its elaborate blue tiles and cascading domes and better known as the Blue Mosque.
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Benedict had visited Turkey amid heightened Christian-Muslim tensions and prayed at the mosque in a gesture that was appreciated by many Turks.
The Vatican added the stop at the Blue Mosque at the last minute to show Benedict's respect for Muslims. Francis then visited the nearby Haghia Sofia, which was the main Byzantine church in Constantinople present-day Istanbul before being turned into a mosque following the Muslim conquest of the city in 1453.
Pope Paul VI, who made the first-ever papal visit to Turkey in 1967, fell to his knees in prayer inside Haghia Sophia, triggering protests by Turks who claimed Paul had violated the secular nature of the domed complex.
All eyes were turned on Francis to see if he would do the same but careful of Turkish sensitivities, the pope avoided praying inside the Haghia Sophia.
Halfway through his tour, the Muslim call for prayer from the Blue Mosque echoed off the Haghia Sophia's marble walls, drowning the voice of the museum's director who escorted Francis around the structure.