Presiding over the Requiem Mass in St Peter's Square, the 91-year-old prelate delivered a message both political and pastoral.
"A person who thinks only about building walls, wherever they may be, and not building bridges, is not Christian", he told the crowd, echoing Francis's criticism of US President Donald Trump's immigration policies first voiced in 2016.
Mr Trump, who clashed publicly with the Pope over migrant compassion, sat just yards from the altar.
Ukrainian President Volodymyr Zelensky, who had not confirmed if he would attend, appeared to receive a round of applause when he stepped out of St Peter's Basilica. The crowd of assembled world leaders clapped as he walked down the steps into St Peter's Square.
88-year-old Pope Francis, who died on Easter Monday, has been hailed for his leadership of the Church, proving popular among young people and known for his outreach to those most in need in society.
As the funeral began, thousands of mourners and visiting dignitaries fell silent as a simple wooden casket, topped with a large cross, was carried into view by a dozen pallbearers.
Reflecting on the Pope's final public appearance on Easter Sunday, Cardinal Re told the assembled crowd: "Despite his serious health problems, he wanted to give us his blessings from the balcony of St Peter’s Basilica, then came down to greet us from his open Popemobile as a large crowd gathered for the Easter Mass."
Giving a homily in Italian, he highlighted the late pontiff's lifelong call for peace.
"War always leaves the world worse than it was before: it is always a painful and tragic defeat for everyone," he said.
Cardinal Re also praised Francis's "charisma of welcome and listening" and his efforts to shed "light on the problems of our time with the wisdom of the gospel".
As the service drew to a close, the crowd applauded as the pontiff’s coffin was brought back into St Peter’s Basilica - the first pope in more than a century not to be entombed there.
Instead, he has chosen the Santa Maria Maggiore Basilica as his final resting place, a fifth-century church located in the centre of Rome that already holds the tombs of seven popes.