Addressing tens of thousands of people in St Peter's Square on Palm Sunday, the celebration that opens the holiest week of the year in the lead-up to Easter for the world's 1.4 billion Catholics, the pontiff said Jesus could not be used to justify any wars.
"This is our God: Jesus, King of Peace, who rejects war, whom no one can use to justify war," the first US Pope told crowds in brilliant sunshine.
"(Jesus) does not listen to the prayers of those who wage war, but rejects them, saying: 'Even though you make many prayers, I will not listen: your hands are full of blood'," he said, citing a passage from the Bible.
Leo did not specifically name any world leaders, but he has been ramping up criticism of the Iran war in recent weeks.
During an appeal at the end of Sunday's celebration, the Pope lamented that Christians in the Middle East "are suffering the consequences of an atrocious conflict" and might not be able to celebrate Easter.
The Pope, who is known for choosing his words carefully, has repeatedly called for an immediate ceasefire in the conflict and said on Monday military air strikes were indiscriminate and should be banned.
Some US officials have invoked Christian language to justify the joint US-Israeli strikes on Iran on February 28 that initiated the expanding war.
US Defense Secretary Pete Hegseth, who has started leading Christian prayer services at the Pentagon, prayed at a service on Wednesday for "overwhelming violence of action against those who deserve no mercy".
In his homily on Sunday, Leo referenced a Bible passage in which Jesus, about to be arrested ahead of his crucifixion, rebuked one of his followers for striking the person arresting him with a sword.
"(Jesus) did not arm himself, or defend himself, or fight any war," Leo said.
"He revealed the gentle face of God, who always rejects violence. Rather than saving himself, he allowed himself to be nailed to the cross."
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