Ahead of Saturday's title showdown, the two teams had been level on 63 points at the top of the table, with PSG leading on goal difference, but with seven games to go Lille looks in pole position to win Ligue 1 for the first time in a decade.
It's the first time in a quarter of a century that Lille has beaten PSG in the capital, with Canadian Jonathan David scoring the winner in a 1-0 victory as the Parisians slumped to a third successive home defeat.
David struggled with an ankle injury after being caught by Idrissa Gana Gueye during his game winner and Lille's goalscorer was unable to play on, watching from the sidelines on crutches as the visitors held on for victory.
In the game's closing stages, Neymar clashed with Lille's Tiago Djalo and, with both players on yellow cards, they were red carded by referee Benoît Bastien in the 90th minute and stoppage time.
Recently troubled by an adductor injury, Neymar had last started a Ligue 1 game for PSG on January 31.
Saturday's result moved Lille three points clear of PSG, while Monaco is in third on 62 points after beating Metz 4-0.
"We are top and we are in the fight, but so are Lyon, Paris and Monaco. There is not much in it," Lille coach Christophe Galtier told reporters.
Lille had lost their previous two matches coming into Saturday's game, including a surprise defeat by Nîmes, but Galtier's team will drew confidence for the run-in having only suffered fewer losses than only Atletico Madrid and Inter Milan (two defeats) in Europe's top five leagues.
The win over PSG also ensured Lille recorded their 18th clean sheet in 31 league games.
PSG faces Bayern Munich on Wednesday in the Champions League quarterfinals.
"I am disappointed with the result and at losing three important points, said Mauricio Pochettino after the defeat by Lille. "I am not worried but we will need to keep fighting to the end.
"We are an inconsistent side for lots of reasons but we are working to fix that."