In a highly symbolic gesture, the pope climbed a ramp facing the Rio Grande that separates Mexico's Ciudad Juarez and El Paso, Texas, laid flowers under a black cross and blessed hundreds of migrants on the American side, who waved at him.
Francis then celebrated mass with more than 300,000 Catholic faithful on the Juarez side of the border, with tens of thousands more watching it on a giant screen in an El Paso stadium.
But the first Latin American pontiff did not directly address the politics across the border, focusing instead on the plight of migrants.
"We cannot deny the humanitarian crisis which in recent years has meant the migration of thousands of people, whether by train or highway or on foot, crossing hundreds of kilometres through mountains, deserts and inhospitable zones," Francis said.
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"The human tragedy that is forced migration is a global phenomenon today."
Central Americans have been leaving their poor and gang- infested countries in droves, crossing Mexico's porous southern border with Guatemala on their way to the United States.
Thousands have died while crossing the scorching US-Mexico desert in the past two decades, according to official figures.
"Injustice is radicalised in the young; they are cannon fodder, persecuted and threatened when they try to flee the spiral of violence and the hell of drugs. Then there are the many women unjustly robbed of their lives," Francis said in a city that has been scarred by gang wars and unexplained murders of women.
"No more death. No more exploitation. There is still time to change, there is still a way out and a chance, time to implore the mercy of God," he said before flying back to Rome after a five-day trip to Mexico.
Trump, who wants Mexico to pay to build a wall along the border, has called the pope a "very political person.