After praying at the blast site, the Pope celebrated the final Mass of his trip in front of an estimated 150,000 people gathered on Beirut's waterfront.
Addressing the crowd, he lamented that the beauty of Lebanon had been "overshadowed by poverty and suffering, the wounds that have marked your history".
But he appealed to the country's diverse communities to unite to solve its problems.
"Let us cast off the armour of our ethnic and political divisions, open our religious confessions to mutual encounter and reawaken in our hearts the dream of a united Lebanon," he said. "A Lebanon where peace and justice reign, where all recognise each other as brothers and sisters."
Since the last papal visit in 2012, the small country has been plagued by multiple crises.
In 2019, the country suffered one of the worst economic depressions recorded in modern times, which pushed millions into poverty.
It was followed by mass anti-government protests, the coronavirus pandemic, and then the Beirut port explosion.
Political paralysis prevented the country from passing the economic and structural reforms demanded by foreign donors in return for billions of dollars in aid.
Lebanon was later devastated by the 13-month war between the Shia Muslim Hezbollah movement and Israel, which killed 4,000 Lebanese and 120 Israelis.
A ceasefire ended the conflict a year ago, but Israel has continued to attack targets it says are linked to Hezbollah, accusing the Iran-backed group of trying to rearm.