On the final day of a week-long tour of Spain, in which the pontiff has urged global leaders to treat migrants more humanely, Leo said he wanted to directly address those who "take advantage of peoples' desperation (or) organise death routes".
"Stop. Repent," the first US pope said on Friday.
"For every life lost, every family deceived ... you will have to appear before divine justice."
"Repent while there is still time," he said, invoking the Catholic belief that someone who did evil in life must confess their sins and make amends or be sent to hell in death.
Leo, who has been more outspoken in his criticism of the direction of global leadership in recent months, is visiting the Canary Islands, a Spanish archipelago off the western coast of Africa, as the culmination of his three-stop tour of Spain.
The islands are one of the main gateways into Europe for migrants, who risk taking a deadly journey through Atlantic waters, often in improvised and overcrowded small craft.
On Thursday, his first of two days on the islands, the pope warned world leaders that history would condemn those who allowed people fleeing war or poverty to suffer.
In a meeting with charities helping migrants on Friday, Leo said the "tears and blood" of migrants who were exploited trying to reach Europe "cry out to God".
He was speaking on the day the EU's Migration Pact, which tightens rules on asylum, comes fully into force.
More than 1000km from mainland Spain, the Canaries saw migration peak in 2024, when the islands received 46,843 irregular migrants, compared with fewer than 1000 in 2015, according to official data.
More than 3000 people died in 2025 trying to reach the islands, according to the NGO Caminando Fronteras.
Leo, who started his tour in Madrid, was the first pope to address the Spanish parliament, where he warned that escalating conflicts were pushing the world into a profound crisis.
He also visited Barcelona, where he inaugurated the newest of the soaring geometric spires of the Sagrada Familia, now the world's tallest church.
Crowds during Leo's visit have been large.
More than 1.2 million thronged one of Madrid's main squares in intense heat to see the pontiff on Sunday, in the largest event yet of his year-long papacy.
Spending Friday on Tenerife, the pope also heard testimonies from several migrants during a visit to an interim housing centre that has received some 70,000 migrants since it opened in 2021.
Leo was due to depart for Rome in the afternoon.
