Valenciennes, St Etienne, Montpellier and Arles-Avignon were also eliminated by lower-league opposition, making it nine top-flight teams that have already gone out.
Paris Saint-Germain, however, recorded a 5-1 demolition of fellow Ligue 1 team RC Lens who were playing their first competitive game under new coach Laszlo Boloni.
Ligue 1 leaders Lille eased past fifth division Forbach, goals by Eden Hazard, Aurelien Chedjou and Gervinho earning a 3-1 away win.
Olympique Lyon needed a second-half goal by Pape Diakhate to triumph 1-0 at Caen.
Remy Sahinovic put Chambery on the football map as the fifth division side knocked out Monaco 3-2 on penalties while Gregoire Debuchy and David Coulibaly helped Wasquehal beat Auxerre 2-1.
Sahinovic converted the last penalty in a tense shootout after the game had ended in a 1-1 draw.
HANDBALL TEAM
"It's wonderful," the 26-year-old Sahinovic told Eurosport. "When I'm about to take a penalty, I think only about scoring.
"After handball and skiing, now there is some football in Chambery."
Chambery is best known for its handball team, regulars in the Champions League, and surrounding ski resorts.
Wasquehal, who also play in the fifth division, live in Lille's shadow and they were inspired after being loaned the stadium belonging to the Ligue 1 leaders.
Auxerre, who played in the Champions League this season, looked set for a routine win after Adama Coulibaly opened the scoring in the 12th minute.
Wasquehal hit back with 10 minutes left through Debuchy before David Coulibaly converted a penalty two minutes from time.
Ligue 1 side Nice avoided an embarrassing defeat at third division Creteil when keeper Lionel Letizi helped them to a 6-5 penalty shootout victory following a 1-1 draw.
Toulouse, another Ligue 1 side, were beaten 2-1 by third division Paris FC on Friday.
