The result left PSG top on 36 points, 11 ahead of second-placed Lille. Third-placed Montpellier, who are a further three points adrift, host fifth-placed Olympique de Marseille in the round's other standout fixture on Sunday.
Mbappe lit up the match with another brilliant goal, his 11th of the season, when he took a through ball in his stride and buried a delightful curling shot from 20 metres past Lille keeper Mike Maignan in the 70th minute.
Neymar made it 2-0 with a clinical finish in the 84th after before Nicolas Pepe netted a stoppage-time penalty for Lille, who matched the home side for long spells with an adventurous approach and incisive passing.
PSG always looked more dangerous, though, as Mbappe went close with a low shot in the 10th minute before Maignan denied Angel Di Maria from close range and Brazilian defender Marquinhos headed over the bar following a corner.
Thomas Meunier fired high after a dazzling run by Mbappe and Maignan again rescued Lille with two good saves as Lille were forced to hang on in the closing stages of the first half.
Two darting raids by PSG came to nothing shortly after halftime as crisp one-touch passing lacked a finishing touch before Mbappe broke the deadlock with lethal precision.
Maignan did well to block Marco Verrati;s shot from six metres before Neymar drilled in the second for PSG, who then conceded a clumsy penalty as one of their defenders needlessly handled the ball.
Pepe blasted the spot-kick past Gianluigi Buffon into the top corner but Lille ran out of time to force a draw.
(Writing by Zoran Milosavljevic; Editing by Ed Osmond)
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