Leo, the first US-born pope, emphasised Easter's message of hope as a celebration of Jesus' resurrection after being crucified.
"Let us allow our hearts to be transformed by his immense love for us! Let those who have weapons lay them down! Let those who have the power to unleash wars choose peace! Not a peace imposed by force, but through dialogue! Not with the desire to dominate others, but to encounter them!" the pope said.
With the US-Israeli war on Iran in its second month and Russia's ongoing campaign in Ukraine, Leo acknowledged a sense of indifference "to the deaths of thousands of people ... to the repercussions of hatred and division that conflicts sow … to the economic and social consequences they produce.''
Without mentioning the wars by name, Leo quoted his predecessor, Pope Francis, who during his last public appearance from the same loggia last Easter reminded the faithful of the "great thirst for death, for killing, we witness each day".
Francis, weakened by a long illness, died the next day on Easter Monday.
The Urbi et Orbi blessing, Latin for "to the city and the world,'' has traditionally included a litany of the world's woes.
Leo followed that formula during his Christmas blessing. There was no immediate explanation for the shift.
Earlier, Leo addressed some 50,000 faithful from an open-air altar in St Peter's Square flanked with white roses while the steps leading down to the piazza where the faithful gathered were filled with spring perennials, symbolically resonating with the pope's words.
He implored the faithful in his homily to keep their hope in the face of death, which lurks "in the abuses that crush the weakest among us, because of the idolatry of profit that plunders the earth's resources, because of the violence of war that kills and destroys.''
Speaking from the loggia, the pope announced a prayer vigil for peace April 11 in the basilica.
Before retreating into the basilica, Leo stepped forward out of the loggia's shadow and waved to the cheering crowd below.
He later greeted people in the piazza from the popemobile that took him all the way down Via della Conciliazione toward the Tiber River and back.
During the marathon that is Holy Week, Leo also reclaimed the tradition of washing priests' feet on Holy Thursday, a gesture of encouragement toward clergy.
Francis had chosen a more inclusive path, travelling to prisons and homes for the disabled to wash the feet of women, non-Christians and prisoners.
The 70-year-old pontiff also became the first pope in decades to carry the light wooden cross for the entire 14 stations during the Way of the Cross on Good Friday.
