The first season of Marsupilami premiered on 18 March 2000, on Canal J. Produced by Cactus Animation, Marathon Production, and Marsu Productions. This series is far more faithful to the original Marsupilami comic series than the previous Marsupilami animated works made by Disney (featured in the 1992 series Disney's Raw Toonage and its spin-off). In this first season, Marsupilami went on adventures alone or with his family (his wife Marsupilamie and their 3 young children, Bibi, Bibu, and Bobo).

Marsupilami and his family become best friends with a human family, the Du Jardin, that comes to live near them. Amanda is a Marsupilami researcher, while her husband Jean-Pierre is a computer technician that works from home and they have two children, Teo and Zoe. Teo and Marsupilami become best friends and they have lots of adventures, with both new friends and old enemies, like Backalive.

Features a preteen boy named Hector and his aunt Diane, who are going to live in the jungle for one year to study its fauna and flora. They become best friends with the Marsupilami family. Their main enemies are megalomaniac industrialist and jungle-hater Felicia Devort, who plans to level out the Palombian jungle and build the Devort City megalopolis in its place, and her two henchmen, Stroy and Blouprint.

The final season featured the Marsupilami family living with veterinarian Bernard Vanderstadt and his 4 children: Sarah, Iris, Isidore, and Zoe. Their mother, Caroline, frequently contacts them by phone, but appears in the last 3 episodes. Once again, Backalive makes an appearance.