In a letter to US bishops, Francis, 88, said deporting people who had fled their own countries in distress "damages the dignity" of the migrants and could leave many vulnerable and defenseless.
"I exhort all the faithful of the Catholic Church, and all men and women of goodwill, not to give in to narratives that discriminate against and cause unnecessary suffering to our migrant and refugee brothers and sisters," he wrote.
The letter, published by the Vatican, sparked a swift retort from the Trump White House.
"I wish he'd stick to the Catholic Church and fix that and leave border enforcement to us," the president's border czar, Tom Homan, told reporters.
"He wants to attack us for securing our border? He's got a wall around the Vatican, does he not?... We can't have a wall around the United States."
Homan also noted that he is a "lifelong Catholic" himself.
The tiny Vatican City state is located in the middle of Rome, surrounded by a high wall punctuated by gates manned by the pontiff's Swiss Guard.
- 'End badly' -
Francis has repeatedly defended the rights of migrants during his 10 years leading the Catholic Church, urging world leaders to be more welcoming to those fleeing poverty or violence.
And he warned as Trump returned to the White House last month that the Republican's pledge to carry out the largest deportation campaign in US history, by expelling millions of undocumented immigrants, would be a "calamity".
"I have followed closely the major crisis that is taking place in the United States with the initiation of a programme of mass deportations," the Argentine pontiff wrote Tuesday.
He acknowledged "the right of a nation to defend itself and keep communities safe from those who have committed violent or serious crimes while in the country or prior to arrival".
But he wrote that "the act of deporting people who in many cases have left their own land for reasons of extreme poverty, insecurity, exploitation, persecution or serious deterioration of the environment, damages the dignity of many men and women, and of entire families".
Deportation "places them in a state of particular vulnerability and defenselessness", he wrote.
"This is not a minor issue -- an authentic rule of law is verified precisely in the dignified treatment that all people deserve, especially the poorest and most marginalized," he continued.
He added: "This does not impede the development of a policy that regulates orderly and legal migration. However, this development cannot come about through the privilege of some and the sacrifice of others.
"What is built on the basis of force, and not on the truth about the equal dignity of every human being, begins badly and will end badly."
Francis has criticized Trump for his anti-migrant policies in the past.
In February 2016, when asked about the then-US presidential hopeful's stance, the pope said: "Anyone, whoever he is, who only wants to build walls and not bridges is not a Christian".
And last year Francis made a rare foray into the US election season to call harsh anti-migrant attitudes "madness" and criticise right-wing US Catholic figures for overly conservative stances.
In May 2017, when Trump was in his first term, he was received at the Vatican for a half-hour meeting.
© Agence France-Presse
