The French striker, linked with a move to Real Madrid in the summer, received the ball down the left from a deft backheel from Neymar, and weaved between two defenders inside the box before slicing through the legs of Thibaut Courtois to drive Parque de los princes.
It was a dramatic end to a game that seemed destined to end in frustration for PSG, especially after Lionel Messi had his penalty saved just after the hour mark.
The hosts had dominated possession but struggled to break down a well-organized Real Madrid defense that had limited PSG to one shot on goal in the first half, when Mbappe saw a shot denied by Courtois’s legs.
But the incorporation of Neymar, who had made his debut since November after recovering from an injury, was decisive. He caused Real a number of problems with his dangerous crosses and clever runs before providing the crucial pass for Mbappe to work magic on him with seconds remaining.
Victory will give PSG hope that they can travel to Madrid on Wednesday 9 March and get the result they need to keep their hopes of winning a first Champions League title alive.