"Both are against life, be it the one who kicks out migrants or the one who (supports) killing babies," Francis said.
"Both are against life," Francis told reporters aboard his plane returning to Rome after a 12-day tour of Asia.
Francis stressed that he is not an American and would not be voting.
Neither the Republican candidate Donald Trump nor the Democratic candidate Kamala Harris was mentioned by name.
But Francis nevertheless expressed himself in stark terms when asked to weigh in on their positions on two hot-button issues in the US election - abortion and migration - that are also of major concern to the Catholic Church.
Francis has made the plight of migrants a priority of his pontificate and speaks out emphatically and frequently about it.
While strongly upholding church teaching forbidding abortion, Francis hasn't emphasised church doctrine as much as his predecessors.
He said that migration is a right described in scripture, and that anyone who doesn't follow the Biblical call to welcome the stranger is committing a "grave sin".
He was also blunt in speaking about abortion.
"To have an abortion is to kill a human being. You may like the word or not, but it's killing," he said.
"We have to see this clearly."
Asked though what to do at the polls, Francis recalled the civic duty to vote.
"One should vote, and choose the lesser evil," he said.
"Who is the lesser evil, the woman or man? I don't know."
"Everyone in their conscience should think and do it," he said.
It's not the first time Francis has weighed in on a US election.
In the run-up to the 2016 election, Francis was asked about Trump's plan to build a wall at the US-Mexican border.
Francis declared then that anyone who builds a wall to keep out migrants "is not Christian".
In responding on Friday, Francis recalled that he celebrated Mass at the US-Mexico border and "there were so many shoes of the migrants who ended up badly there".
The US bishops conference, for its part, has called abortion the "preeminent priority" for American Catholics in its published voter advice. Harris has strongly defended abortion rights.
US President Joe Biden, an observant Catholic, shares Harris' strong support for abortion rights, a stance that prompted some Catholic bishops and other conservatives to call for him to be denied access to Communion.
After meeting Francis in person at the Vatican in October 2021, Biden came away saying the pope told him he was a "good Catholic" and should continue receiving Communion.
Francis, asked on previous occasions about some US bishops who want to deny Communion to Biden over his support for abortion rights, has said bishops should be pastors, not politicians.