Argentine striker Lisandro, struggling for form after injury problems, netted each side of the interval to inflict Lille's first league defeat of the season.
Lyon, who won the French title seven years in a row from 2002, climbed to 14th place with 11 points from nine matches, eight behind Stade Rennes following their goalless draw at struggling RC Lens earlier on Sunday.
"We showed great character, it's a well-deserved win," coach Claude Puel told French TV channel Canal Plus. "We're finding our stride."
At Lyon's Gerland stadium, Lisandro put the hosts ahead after only three minutes, firing past Mickael Landreau with a powerful strike from just outside the box.
France playmaker Yoann Gourcuff, who scored twice in Les Bleus' back-to-back victories in Euro 2012 qualifiers against Romania and Luxembourg, made it two four minutes before half-time.
Unbeaten Rennes extended their Ligue 1 lead despite being held goalless at Lens's Felix Bollaert stadium.
"It's a good draw. We were better in the first half but we relaxed too much after the break," Rennes midfielder Yann Mvila told the French TV channel Foot Plus.
"We had to stop losing, three points would have been better but in our situation, one point is fine," Lens captain Eric Chelle said.
France striker Dimitri Payet, the league's top scorer, netted his eighth goal of the campaign from the penalty spot. Nice, however, piled on the pressure after the break and Anthony Mounier equalised with a volley.
