The first US pope chose mainly Muslim Turkey as his first overseas destination to mark the 1700th anniversary of a landmark early Church council there that produced the Nicene Creed, still used by most of the world's Christians today.
Leo landed in the capital Ankara on Thursday for what is a crowded three-day itinerary in Turkey before heading on to Lebanon.
It will be closely watched as he makes his first speeches overseas and visits sensitive cultural sites.
"It's a very important trip because we do not know much yet about Leo's geopolitical views, and this is the first big chance for him to make them clear," Massimo Faggioli, an Italian academic who follows the Vatican, told Reuters.
Foreign travel has become a major part of the modern papacy, with popes attracting international attention as they lead events with crowds sometimes in the millions, give foreign policy speeches and conduct international diplomacy.
Leo was elected in May by the world's Catholic cardinals to succeed the late Pope Francis.
A relative unknown on the world stage before his election, Leo spent decades as a missionary in Peru and only became a Vatican official in 2023.
Francis had been planning to visit Turkey and Lebanon but was unable to go because of his worsening health.
Leo, 70, was scheduled to meet President Recep Tayyip Erdogan and address political leaders in the Turkish capital.
He will fly on Thursday evening to Istanbul, home to Patriarch Bartholomew, spiritual leader of the world's 260 million Orthodox Christians.
Orthodox and Catholic Christians split in the East-West Schism of 1054, but have generally sought in recent decades to build closer ties.
Leo and Bartholomew travel on Friday to Iznik, 140km southeast of Istanbul and once called Nicaea, where early churchmen formulated the Nicene Creed, which lays out what remain the core beliefs of most Christians today.
In a departure from normal practice - popes usually speak Italian on foreign trips - Leo is expected to speak English in his speeches in Turkey.
Peace is expected to be a key theme of the Pope's visit to Lebanon, which starts on Sunday.
Lebanon, which has the largest percentage of Christians in the Middle East, has been rocked by the spillover of the Gaza conflict as Israel and the Lebanese Shi'ite Muslim militant group Hezbollah went to war, culminating in a devastating Israeli offensive.
Last Sunday, Israel killed the top military official in Iran-backed Hezbollah in an airstrike on a southern suburb of the Lebanese capital Beirut despite a year-long, US-brokered truce.
Vatican spokesman Matteo Bruni said on Monday that necessary security precautions were being taken to ensure the pope's safety in Lebanon, but he would not comment on specifics.
