Leo Berdeu kicked a late penalty to give Lyon their first ever French Top 14 win at Bordeaux-Begles, 22-20, retook first place with a bonus point.
Fly-half Berdeu slotted over from the tee with seconds remaining to hand the in-form home side their first defeat of the season on their own turf.
Bordeaux-Begles edged past Toulouse for top spot on their head-to-head record after the champions had earlier climbed into first with a 27-20 win over Montpellier.
Stuart Hogg's avoidable error helped the record 23-time champions to victory. The Former Scotland captain failed to gather a kick near his own line, gifting Toulouse centre Dmitri Delibes the easiest of tries.
Toulouse were without 10 players away with France's squad preparing for the upcoming Six Nations, including superstar scrum-half Antoine Dupont.
Test centurion Hogg, 32, was playing his first game since being sentenced by a Scottish court to a year of supervision, having avoided jail after admitting he had abused his estranged wife over five years.
Hogg's fellow Scot, Toulouse winger Blair Kinghorn had a better time, crossing for his fourth try of the season a week out from a likely start in Scotland's first Six Nations game against Italy.
"We played more intelligently in the second half," Toulouse backs coach Clement Poitrenaud told reporters.
"It's nice to coach this inexperienced team because they want things, they're hungry," the former France back added.
Elsewhere, Racing 92 extended their Top 14 run without a win to six matches as they were beaten 27-20 by Castres to pile pressure onto head coach Stuart Lancaster.
The Parisians' former back-rower and two-time Rugby World Cup-winning captain Siya Kolisi was in the stands after he left the club to return home to South Africa with Durban's Sharks last year.
"It's up to us to think about how we can stay in the Top 14," Racing assistant coach Frederic Michalak told Canal+ with his side just two points above the relegation play-off berth.
"Our standard today, collectively and individually, was not at the standard of the Top 14. We have to be much better than that," the former France half-back added.
In a battle between the league's two bottom sides, 14th-placed Vannes edged Stade Francais 33-28.