Second half goals from Nicolas Pépé, Jonathan Bamba, Gabriel dos Santos Magalhaes and Jose Fonte gave Lille a resounding victory.
It was PSG's heaviest league defeat since Qatar Sports Investment (QSI) took over the club in 2011.
It was a night to forget all round for PSG, who had two Mbappe goals ruled out for offside and lost captain Thiago Silva and Meunier to injury in the first half.
Lille went ahead after Meunier diverted a Jonathan Ikone cross into his own goal in the seventh minute.
However, the Spanish full-back was shown a straight red card shortly before the break when he brought down Pepe as the striker was rushing towards goal.
Debuchy then completed the win with a deflected close-range strike in the final minute to put Jean-Louis Gasset's side back ahead of Marseille, who started the day fourth and in the Europa League spot after surviving late VAR penalty drama on Saturday to scrape to a 2-1 win over Nimes.
Mbappe tormented the Lille defence but he was isolated up front and it was Lille who scored another, in the 65th when Bamba out-paced the defence and beat goalkeeper Alphonse Areola. Arsenal and Bayern Munich have also been touted as Pepe's next destination should he leave Lille this summer, and Lille chief Lopez has now all but confirmed his club's stat player will depart in the coming months.
Mbappe could be heard complaining about the referee, saying per French Football News: "This referee takes the Coupe de la Ligue from us, he takes our players from us, he takes everything".
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"We're going to be champions but we can not lose like this".
"That's not normal. We have to show more personality, that's one of our faults and we have to fix that. We played like beginners here".
PSG coach Thomas Tuchel, however, was quick to disagree with Mbappe's comments.
Tuchel only had six substitutes on his bench for the 5-1 defeat.
"Four or five players will leave this summer".
"Moussa Diaby has played only twice and (Thilo) Kehrer is sick - ordinarily they should not be with us, but here we are".
"We can not go over the top either, people are going to talk about the club, I don't know what else. To win here, we would have needed more quality".