"Terrible news comes to us from Syria with dozens of victims, many of them women and children ... so many people are struck by the effects of the chemical substances in the bombs," the pope told thousands of people gathered in St Peter's Square.
"There is not a good war and a bad one, and nothing, nothing can justify the use of such devices of extermination against defenceless people and populations," he added.
Renewed air strikes have hit Douma, the last rebel-held town near Damascus, where first responders accused forces loyal to President Bashar al-Assad of using "poisonous chlorine gas" in attacks on Saturday.
"Pray for political and military leaders to choose the other path, that of negotiation, the only one that can bring peace that is not that of death and destruction," the pope said.
Syrian state media, quoting an official source, has said reports of chemical weapons use were rebel "fabrications".
Russia, one of the Syrian regime's main allies, has also dismissed the allegations.