Pope Leo XIV stepped into the international political arena at evening prayers in St Peter’s Basilica in Vatican City on Saturday, saying prayer for peace is “a bulwark against that delusion of omnipotence that surrounds us and is becoming increasingly unpredictable and aggressive.”

The first US-born pope said: “Even the holy Name of God, the God of life, is being dragged into discourses of death.”

Addressing world leaders who decide to go to war, Leo said: “To them we cry out: stop! It is time for peace! Sit at the table of dialogue and mediation – not at the table where rearmament is planned and deadly actions are decided.”

“Enough of the idolatry of self and money! Enough of the display of power! Enough of war! True strength is shown in serving life,” he added.

While the pope did not explicitly mention the US-Israeli war with Iran, or name any single country or president, his words will be read as his strongest condemnation yet of a conflict the US defense secretary, Pete Hegseth has cast as a sacred struggle. The pope’s remarks came during face-to-face negotiations between US and Iranian delegations in Pakistan to shore up a fragile truce and put a permanent end to hostilities.

The US delegation in Islamabad was led by JD Vance, the vice-president, whose new book is about his conversion to Catholicism. The talks take place days after it was reported that Vance’s friend, Elbridge Colby, a senior Pentagon official who is also Catholic, had summoned the Vatican’s ambassador to the US in January to rebuke him over comments by the pope that month. Leo’s January declaration that “a diplomacy that promotes dialogue and seeks consensus among all parties is being replaced by a diplomacy based on force” reportedly enraged Pentagon officials.

Leo’s tone and message on Saturday appeared aimed at Trump administration officials, who have boasted of US military superiority and justified the war in religious terms.

Defense secretary Pete Hegseth has invoked his Christian faith to cast the US as a Christian nation righteously seeking to vanquish its foes, describing the attack on Iran as a holy war carried out “in the name of Jesus Christ” and even compared the rescue of a downed F-15 airman in terms that echoed the resurrection of Jesus.

The pope said that those who pray “are aware of their own limitations. They do not kill or threaten with death. Instead, death enslaves those who have turned their backs on the living God, turning themselves and their own power into a mute, blind and deaf idol, to which they sacrifice every value, demanding that the whole world bend its knee.”

As the Letters from Leo newsletter reported, the pope offered his homily at the tomb of St Peter at a prayer vigil announced during the pope’s Easter Urbi et Orbi message. He was joined by parishes on every continent, and thousands to St Peter’s Basilica for an evening of rosary and meditation.

The effort to contest any religious justification for war was made before emissaries from both the US and Iran: in the basilica pews were Laura Hochla, deputy chief of mission with the US embassy to the Holy See, and the archbishop of Tehran, Belgian cardinal Dominique Joseph Mathieu.

At the start of the war in six weeks ago, Chicago-born Pope Leo seemed initially reluctant to publicly condemn the violence and limited his comments to muted appeals for peace and dialogue.

But on Palm Sunday he stepped up criticism and later said that Donald Trump’s threat on Easter Sunday to annihilate Iranian civilization was “truly unacceptable”.

On Friday, Leo wrote on his official X account: “God does not bless any conflict. Anyone who is a disciple of Christ, the Prince of Peace, is never on the side of those who once wielded the sword and today drop bombs. Military action will not create space for freedom or times of #Peace, which comes only from the patient promotion of coexistence and dialogue among peoples.”

The pope also wrote: “Absurd and inhuman violence is spreading ferociously through the sacred places of the Christian East. Profaned by the blasphemy of war and the brutality of business, with no regard for people’s lives, which are considered at most collateral damage of self-interest. But no gain can be worth the life of the weakest, children, or families. No cause can justify the shedding of innocent blood.”