Francis met Muscat and his wife and family on Saturday morning, the Vatican said, in an audience that was far more low-key than those normally held with heads of government.
Unusually, no journalists were allowed to cover the event, which a Vatican spokesman said had been scheduled months ago.
Muscat said on Sunday he would resign as leader of the ruling Labour Party on Jan. 12 and in "the days after" will quit as prime minister. Opponents said he should go immediately.
A group of 22 Maltese academics sent a letter to the Vatican dated Nov. 27, before Muscat announced he would resign, urging the pope to cancel the meeting to avoid what they called a "propaganda exercise" in favour of Muscat.
The political stability of the tiny Mediterranean island has been rocked in recent weeks by the fallout from the 2017 murder of anti-corruption journalist Daphne Caruana Galizia, who was blown up by a car bomb.
Muscat is not directly implicated in the investigation, which has made rapid progress in the last few weeks, but the self-confessed middleman in the murder plan has linked people in the premier's inner circle to attempts at a cover-up.