Pope Benedict XVI appealed for leaders in the Middle East to work for peace and reconciliation and urged those at the service to “be peacemakers”.
The pontiff also renewed his call for a end to the violence in Syria.
He later left Lebanon, after a ceremony at Beirut airport attended by flag-waving crowds.
The visit came amid anti-US protests in the region over a film deemed insulting to Islam.
It was the first papal trip to Lebanon since John Paul II went there in 1997.
An estimated 350,000 worshippers gathered for the waterfront Mass earlier on Sunday. They waved flags and cheered as the Pope made his way through the crowd in his bullet-proof popemobile.
During the service, the Pope urged Christians throughout the Middle East to do their part to end “the grim trail of death and destruction” in the region.
Calling again for peace in Syria, he said: “I appeal to the Arab countries, that, as brothers, they might propose workable solutions respecting the dignity, the rights and the religion of every human person.”
Christians from around Lebanon, as well as Syria, Iraq and further afield, travelled to see him speak in what must have been a very thrilling day.
On Saturday, the pontiff met Lebanese political leaders at the presidential palace near Beirut.
Lebanon’s politicians are bitterly divided over the conflict in neighboring Syria, but the Pope met leaders from across the spectrum, including the Shia Muslim movement Hezbollah.
Addressing an audience of government officials, foreign diplomats and religious leaders, he called for the “fundamental right” of religious freedom to be observed.
Earlier in his visit, the Pope condemned religious fundamentalism and called on all religious leaders in the Middle East “to do everything possible to uproot this threat”.
Controversy over a film deemed to be offensive to the Prophet Mohammed has provoked protests throughout the region since the Pope’s arrival in Lebanon.
The film, Innocence of Muslims, is believed to have been made by a Coptic Christian in the US, and related unrest has led to the death of, among others, the US ambassador to Libya.
The Pope also addressed a gathering of thousands of young people on Saturday, and urged them to stay in Lebanon “and take your place in society and in the Church”.
The number of Christians in the region has been greatly reduced in recent years due to political upheaval and economic pressures.
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