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."
Second-placed St Etienne, trailing Rennes by two points, had Gonzalo Bergessio sent off early in the game as they slumped to a 2-1 defeat at Nice.
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.
Moussa Sow pulled one back for the visitors seven minutes into the second half with an impressive bicycle kick, only for Lisandro to wrap it up from the penalty spot five minutes later.
Midfielder Jeremy Pied was sent off for a second bookable offence 10 minutes from time, forcing Lyon to just sit back and wait for a victory that eased the pressure on Puel.
TEN MEN
Unbeaten Rennes extended their Ligue 1 lead despite being held goalless at Lens's Felix Bollaert stadium.
Rennes were lucky to avoid defeat when keeper Nicolas Douchez superbly parried away a Razak Boukari header from close range eight minutes from time.
They finished with 10 men after Tonga Hamed Doumbia was shown a straight red card for a violent tackle four minutes after coming off the bench.
"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.
Lens still lie second from bottom in the standings.
St Etienne also played with 10 men for almost 70 minutes after striker Gonzalo Bergessio was sent off for a rough tackle.
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.
Midfielder Chaouki Ben Saada made it two in the 67th minute with a powerful shot from just inside the box.
Paris Saint-Germain are third, four points off the pace, following a 2-0 win at Toulouse on Saturday.
