| Date | Day | Competition | Round | Opponent | Venue | Stadium | Attendance | Result | Score | Referee | Notes |
|---|
| 2000-07-29 | Saturday | D1 | 1 | Rennes | H | Stade de Gerland | 33669 | D | 2 | 2 | Alain Hamer | First match for manager: Jacques Santini |
| 2000-08-03 | Thursday | D1 | 2 | Sedan | A | Stade Emile Albeau | 12087 | D | 1 | 1 | Gilles Veissière | |
| 2000-08-07 | Monday | CL | 3rd Prelim. Rnd | Inter Bratislava | A | Štadión Pasienky | 3540 | W | 2 | 1 | Tomasz Mikulski | |
| 2000-08-12 | Saturday | D1 | 3 | Metz | H | Stade de Gerland | 29268 | D | 0 | 0 | Claude Colombo | |
| 2000-08-18 | Friday | D1 | 4 | Bastia | A | Stade Armand Césari | 10300 | L | 0 | 2 | Bruno Derrien | |
| 2000-08-23 | Wednesday | CL | 3rd Prelim. Rnd | Inter Bratislava | H | Stade de Gerland | 20318 | D | 1 | 1 | Roelof Luinge | |
| 2000-08-26 | Saturday | D1 | 5 | Troyes | H | Stade de Gerland | 28103 | W | 1 | 0 | Laurent Duhamel | |
| 2000-09-06 | Wednesday | D1 | 6 | Saint-Étienne | A | Stade Geoffroy-Guichard | 28446 | D | 2 | 2 | Claude Colombo | |
| 2000-09-09 | Saturday | D1 | 7 | Lens | H | Stade de Gerland | 34706 | W | 3 | 0 | Bruno Coue | |
| 2000-09-12 | Tuesday | CL | Group C | Heerenveen | H | Stade de Gerland | 22687 | W | 3 | 1 | Stuart Dougal | |
| 2000-09-17 | Sunday | D1 | 8 | Nantes | A | Stade de la Beaujoire | 26869 | W | 1 | 0 | Pascal Garibian | |
| 2000-09-20 | Wednesday | CL | Group C | Olympiakos | A | Georgios Karaiskakis Stadium | 74000 | L | 1 | 2 | Graham Poll | |
| 2000-09-23 | Saturday | D1 | 9 | Guingamp | H | Stade de Gerland | 32936 | L | 0 | 1 | Patrick Lhermite | |
| 2000-09-27 | Wednesday | CL | Group C | Valencia | A | Estadio Mestalla | 30529 | L | 0 | 1 | Stefano Braschi | |
| 2000-10-01 | Sunday | D1 | 10 | Marseille | A | Stade Vélodrome | 48729 | D | 1 | 1 | Philippe Kalt | |
| 2000-10-17 | Tuesday | CL | Group C | Valencia | H | Stade de Gerland | 38959 | L | 1 | 2 | Paul Durkin | |
| 2000-10-21 | Saturday | D1 | 11 | Bordeaux | A | Parc Lescure | 30107 | D | 1 | 1 | Stéphane Bré | |
| 2000-10-25 | Wednesday | CL | Group C | Heerenveen | A | Abe Lenstra Stadion | 14000 | W | 2 | 0 | Lucilio Cardoso Cortez Baptista | |
| 2000-10-29 | Sunday | D1 | 12 | Auxerre | H | Stade de Gerland | 36339 | D | 2 | 2 | Bruno Ruffray | |
| 2000-11-03 | Friday | D1 | 13 | AS Monaco | A | Stade Louis II | 10408 | W | 2 | 0 | Stéphane Moulin | |
| 2000-11-07 | Tuesday | CL | Group C | Olympiakos | H | Stade de Gerland | 42000 | W | 1 | 0 | Günter Benkö | |
| 2000-11-11 | Saturday | D1 | 14 | Paris Saint-Germain | A | Parc des Princes | 43591 | D | 1 | 1 | Laurent Duhamel | |
| 2000-11-18 | Saturday | D1 | 15 | Lille | H | Stade de Gerland | 32961 | L | 0 | 1 | Gilles Veissière | |
| 2000-11-22 | Wednesday | CL | 2nd Round - Group C | Bayern Munich | A | Olympiastadion | 18000 | L | 0 | 1 | José Maria Garcia-Aranda | |
| 2000-11-25 | Saturday | D1 | 16 | Strasbourg | A | Stade de la Meinau | 14662 | W | 3 | 0 | Pascal Vileo | |
| 2000-11-29 | Wednesday | D1 | 17 | Sedan | H | Stade de Gerland | 28284 | D | 2 | 2 | Bertrand Layec | |
| 2000-12-02 | Saturday | D1 | 18 | Metz | A | Stade Saint-Symphorien | 16218 | D | 0 | 0 | Bruno Coue | |
| 2000-12-05 | Tuesday | CL | 2nd Round - Group C | Spartak Moscow | H | Stade de Gerland | 38404 | W | 3 | 0 | Jose Antonio Marin | |
| 2000-12-09 | Saturday | D1 | 19 | Bastia | H | Stade de Gerland | 35853 | W | 1 | 0 | Pascal Garibian | |
| 2000-12-13 | Wednesday | D1 | 20 | Toulouse | H | Stade de Gerland | 30129 | W | 4 | 1 | Damien Ledentu | |
| 2000-12-13 | Wednesday | CL | 2nd Round - Group C | Arsenal | H | Stade de Gerland | 39518 | L | 0 | 1 | Urs Meier | |
| 2000-12-16 | Saturday | D1 | 21 | Troyes | A | Stade de l'Aube | 13872 | L | 0 | 1 | Bruno Derrien | |
| 2000-12-21 | Thursday | D1 | 22 | Saint-Étienne | H | Stade de Gerland | 39019 | W | 2 | 1 | Alain Sars | |
| 2001-01-06 | Saturday | CDLL | Round of 32 | Sedan | A | Stade Louis-Dugauguez | 10000 | W | 2 | 1 | Claude Colombo | |
| 2001-01-12 | Friday | D1 | 23 | Lens | A | Stade Félix-Bollaert | 38018 | D | 0 | 0 | Bertrand Layec | |
| 2001-01-20 | Saturday | CDF | Round of 64 | Caen | H | Stade de Gerland | 7000 | W | 3 | 2 | Laurent Duhamel | |
| 2001-01-27 | Saturday | D1 | 24 | Nantes | H | Stade de Gerland | 35518 | W | 3 | 1 | Gilles Veissière | |
| 2001-01-31 | Wednesday | CDLL | Round of 16 | Lens | A | Stade Félix-Bollaert | 29943 | W | 3 | 1 | Stéphane Bré | |
| 2001-02-03 | Saturday | D1 | 25 | Guingamp | A | Stade du Roudourou | 13287 | W | 3 | 2 | Bruno Ruffray | |
| 2001-02-06 | Tuesday | D1 | 26 | Marseille | H | Stade de Gerland | 37093 | D | 1 | 1 | Damien Ledentu | |
| 2001-02-10 | Saturday | CDF | Round of 32 | Saint-Étienne | H | Stade de Gerland | 31911 | D | 1 | 1 | Pascal Garibian | aet (Won 4-3 on pens.) |
| 2001-02-17 | Saturday | D1 | 27 | Toulouse | A | Stadium Municipal | 21087 | D | 1 | 1 | Stéphane Moulin | |
| 2001-02-21 | Wednesday | CL | 2nd Round - Group C | Arsenal | A | Highbury | 34303 | D | 1 | 1 | Lubos Michel | |
| 2001-02-24 | Saturday | CDLL | Quarter-Final | Amiens | A | Stade de la Licorne | 10997 | W | 2 | 0 | Bruno Coue | |
| 2001-03-03 | Saturday | D1 | 28 | Bordeaux | H | Stade de Gerland | 35445 | W | 2 | 1 | Alain Sars | |
| 2001-03-06 | Tuesday | CL | 2nd Round - Group C | Bayern Munich | H | Stade de Gerland | 39460 | W | 3 | 0 | Dick Jol | |
| 2001-03-10 | Saturday | CDF | Round of 16 | Fontenay-le-Comte | A | Stade René Gaillard | 10000 | D | 2 | 2 | Patrick Lhermite | aet (Won 5-4 on pens.) |
| 2001-03-14 | Wednesday | CL | 2nd Round - Group C | Spartak Moscow | A | Luzhniki Stadium | 15000 | D | 1 | 1 | Kyros Vassaras | |
| 2001-03-17 | Saturday | D1 | 29 | Auxerre | A | Stade Abbé-Deschamps | 11544 | W | 3 | 0 | Stéphane Bré | |
| 2001-03-31 | Saturday | CDF | Quarter-Final | Strasbourg | A | Stade de la Meinau | 28000 | L | 0 | 3 | Alain Sars | |
| 2001-04-07 | Saturday | D1 | 30 | AS Monaco | H | Stade de Gerland | 35529 | W | 2 | 1 | Bruno Derrien | |
| 2001-04-10 | Tuesday | CDLL | Semi-Final | Nantes | H | Stade de Gerland | 30558 | W | 3 | 2 | Gilles Veissière | |
| 2001-04-15 | Sunday | D1 | 31 | Paris Saint-Germain | H | Stade de Gerland | 38366 | W | 2 | 0 | Stéphane Moulin | |
| 2001-04-28 | Saturday | D1 | 32 | Lille | A | Stade Grimonprez-Jooris | 19466 | W | 2 | 1 | Pascal Garibian | |
| 2001-05-05 | Saturday | CDLL | Final | AS Monaco | N | Stade de France | 78010 | W | 2 | 1 | Stéphane Bré | aet |
| 2001-05-12 | Saturday | D1 | 33 | Strasbourg | H | Stade de Gerland | 40629 | W | 5 | 0 | Bruno Coue | |
| 2001-05-19 | Saturday | D1 | 34 | Rennes | A | Stade de la route de Lorient | 22498 | W | 4 | 3 | Gilles Veissière | |
