Lens had a chance to go top in France for the first time in 16 years but its defensive frailties were ruthlessly exposed by Lille which moves two points ahead of defending champion Paris Saint-Germain.
Burak Yilmaz's low shot put the home side ahead in the echoing, empty Stade Metropole after 11 minutes.
Lens hung on till the second half when Jonathan Bamba scored Lille's second before first Jonathan Gradit and then substitute Clement Michelin were shown red cards as Lens fell apart.
Jonathan Ikone and Yusuf Yazici completed the job for Lille.
"Tonight was a perfect match," said Lille striker Luiz Araujo.
"This start to the season is the result of the hard work we do every day. We are very serious and ready to do a great job but we haven't won anything yet.
"We have to keep our feet on the ground and stay focused on the next game."
Lyon coach Rudi Garcia said his team had "turned the page" after captain Memphis Depay set up three goals in Monday's (AEDT) 3-2 win at Strasbourg to claim its first victory since August.
The Dutch attacker, who was linked with a move to Barcelona during the transfer window, was the provider for Zimbabwe international forward Tino Kadewere and repeated the feat twice for Karl Toko Ekambi in the first half.
Habib Diallo and Jean-Eudes Aholou scored for the hosts but Lyon hung on and move up to ninth with their first three points since August.
"The win was more than deserved. This team had the capacity to admit they had to turn the page," Garcia said.
"The answer was on the pitch, three Depay assists and three goals in open play."
Kadewere opened the scoring after 15 minutes, firing home first time from Depay's long ball.
Depay then combined twice with Toko Ekambi before the 42-minute mark to make it 3-0.
The host fought back as Senegal's Diallo cut the deficit just over a minute later.
Ivory Coast midfielder Aholou, on loan from Monaco, scored with a left-footed volley 10 minutes into the second half.
Meanwhile, Patrick Vieira's Nice side eased to a 3-1 win at Saint-Etienne to move up to fourth, joining Lens on 13 points.
Pierre Lees-Malou opened the scoring for Nice before 20-year-old Amine Gouiri added a second before half-time.
Adil Aouchiche pulled a goal back for Saint-Etienne on 57 minutes but Myziane Maolida sealed the points for the southerner.
On Sunday (AEDT), Marseille warmed up for its return to the UEFA Champions League next week with a 3-1 victory over Bordeaux.