The Pope referred to news of dozens killed, including many children and women, in a suspected poison gas attack on a rebel-held town near the Syrian capital.
He offered prayers for the dead and the families that are suffering.
"There is not a good or a bad war, and nothing can justify such instruments that exterminate defenceless people and populations," Francis said.
"Let's pray that the responsible politicians and military leaders choose another path: that of negotiations, the only one that can bring peace."
Earlier, in a Mass focused on mercy, a signature theme of his papacy, Francis urged the faithful to not give up on the sacrament of reconciliation, especially those who continue to backslide.
He urged the faithful to continue to seek reconciliation, or confession, because "every time we are forgiven, we are reassured and encouraged".
The divine mercy Sunday celebration was established by Pope John Paul II, and this year kicks off a four-day meeting of Francis's Missionaries of Mercy, formed during the recent Holy Year of Mercy to promote confession.
On Tuesday, the missionaries are due to have an audience with Francis, followed by a special Mass with him at St Peter's Basilica.
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