Di Maria got the visitors off to a flying start in the first half before Mbappé sealed the win in the 83rd minute after the home side had two players sent off. Mbappé also set up Mauro Icardi for PSG's fourth goal in injury time.
Mbappé, who recently missed a month with a thigh injury, hadn't played since suffering a reaction to his original injury in Champions League win over Galatasaray on Oct. 1. The win lifts PSG five points clear of Nantes ahead of the rest of the 10th round of matches.
Di Maria opened the scoring in the 15th minute after being sent through all alone from the halfway line by Icardi as Nice's defenders all pushed up. The Argentine stayed cool with only goalkeeper Walter Benitez to beat and picked his spot inside the far corner.
Di Maria's second goal six minutes later was even better as he lifted the ball over Benitez with his first touch from a difficult angle. Marquinhos replaced Brazilian compatriot Thiago Silva for the second half and struck the crossbar with a header from a corner.
A Marquinhos mistake - made while attempting a backpass to Presnel Kimpembe - allowed Ignatius Ganago to pull one back for Nice in the 67th. But the home side's hope of an equalizer were hit in the 74th when Wylan Cyprien was sent off with a second yellow card after he criticized the referee for not awarding a foul against him.
Christophe Herelle followed Cyprien off minutes later with a straight red after the video referee picked up a slap he gave Leandro Paredes, who fell theatrically to the ground.
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