With one game left in Ligue 1, Lyon have 65 points to third-placed Monaco's 62 and also possess a much better goal difference of plus-27 compared to plus-five.
Monaco, who were 2-0 down after eight minutes, had Lacina Traore sent off in the 23rd minute for a second bookable offence.
Champions Paris St Germain have 92 points after Edinson Cavani's treble led them to a 4-0 victory at Gazelec Ajaccio. Zlatan Ibrahimovic also netted his 35th league goal of the season in added time.
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Hosts Lyon went ahead in the third minute thanks to a low cross-shot from Rachid Ghezzal and Lacazette made it 2-0 when he latched on to a cross by Sergi Darder.
Lyon added two more goals before the interval thanks to Mapou Yanga-Mbiwa's header and Lacazette's clever chip.
Monaco pulled one back in the 42nd minute with a Ricardo Carvalho header but Yanga-Mbiwa scored from close range just before the hour and Lacazette bagged his third by tapping in on the rebound after initially being denied by keeper Danijel Subasic.
Nice moved up to fourth on 60 points after Valere Germain's late double gave them a 2-0 win at home to nine-man St Etienne who slipped to fifth with 58 points.
Olympique de Marseille snatched their first league win at the Stade Velodrome since September when Michy Batshuayi's goal helped them beat Stade de Reims 1-0.
(Editing by Tony Jimenez)
