An unexpected late loss suffered by Monaco at Brest earlier in the day offered Lille the chance here to really put pressure on the second-placed principality outfit, but it took less than a minute for Lille to open the scoring.
Home midfielder Tanner Tessmann miscontrolled the ball behind for a corner, and Mitchel Bakker’s resulting delivery was first met by captain Benjamin Andre, with centre-back Bafode Diakite then producing a superb flicked header to put his side in front.
Things soon went from bad to worse for Lyon as Ernest Nuamah was withdrawn due to an injury ironically sustained after he had fouled Gabriel Gudmundsson, with Rayan Cherki taking the Ghanaian’s place.
Lyon could easily have gone 2-0 down on 18 minutes, as another Diakite header from another corner this time flashed wide.
However, Les Gones got back on level terms before half-time following a VAR review as Thomas Meunier was deemed to have handled Lacazette’s header, with the Lyon skipper duly sending Lucas Chevalier the wrong way from the penalty spot.
The hosts now had the wind in their sails, ending the first period arguably the stronger of the teams, with neither Paulo Fonseca - facing his former club for the first time while serving a nine-month touchline ban - or Bruno Genesio making any changes at the break.
Early on after the interval, Lacazette had the chance to double his tally for the evening, but Les Gones’ captain was not able to lob Chevalier from the edge of the box after the Lille goalkeeper’s under-hit pass found Lyon’s talisman.
Lyon goalkeeper Lucas Perri then had a heart-stopping moment as his unorthodox clearance came off the lurking Jonathan David and was shovelled to safety before the Brazilian made an instinctive save to deny the advancing Matias Fernandez-Pardo.
Midway through the second half, Fonseca opted to take off Lacazette as part of a double change, but quickly afterwards, Lyon turned the game on its head as Corentin Tolisso nodded down for Cherki to fire in from around 12 yards out, although Chevalier should have done better.
Aside from Hakon Arnar Haraldsson’s late shot into the arms of Perri, Lille did not produce anything remotely threatening in the closing stages, with Lyon closing out the contest, although Thiago Almada should have made it 3-1 in the 90th minute.
Lyon have now gone four straight meetings without losing for the first time since 2008 and turn their attention to their UEFA Europa League quarter-final first leg against Manchester United, while Lille are next in Ligue 1 action next Saturday at Toulouse.
Flashscore Man of the Match: Corentin Tolisso (Lyon)