Situated at the junction of the Usuthu and Pongola floodplain systems, Ndumo is a good example of a floodplain ecosystem relatively unaffected by human activities. The Pongola River runs through the reserve from south to north while the Usuthu River forms the northern border of the reserve and the international boundary with Mozambique. Associated with these riverine systems are two major shallow seasonal to permanent floodplain pans and many smaller ephemeral pans within the reserve. Water masses in the wet summer months may cover approximately 4 047 ha (40% of the reserve), shrinking to approximately 1 518 ha in the dry season.

The reserve is characterized by a diversity of animal and bird species, many of which are classified as rare or vulnerable. Noteworthy mammal species include red duiker Cephalophus natalensis, hippopotamus Hippopotamus amphibius and suni Neotragus maschatus. At least 415 bird species have been recorded in the reserve, of which at least 73 are rare. Some of these found in the area include the white pelican Pelecanus onocrotalus, openbilled stork Anastomus lamelligerus, yellowbilled stork Mycteria ibis, greater flamingo Phoenicopterus ruber, lesser flamingo P. minor, pygmy goose Nettapus auritus and lesser jacana Microparra capensis. Waterfowl are well represented by a wide variety of species as well as an abundance in numbers. The reserve provides a relatively safe haven for thousands of migrating waterbirds as it sits astride an important north-south migration route. Two Red Data fish species, Nothobranchius orthonotus and Redigobius dewaali and eleven Red Data reptiles and amphibians also occur in the area. This includes a large breeding population of crocodile Crocodylus niloticus.

The Pongola floodplain is of great importance to the local subsistence economy in the region, providing an estimated annual yield of up to 55 tons of fish in the early 1980's. Overfishing in the area outside the reserve has resulted in breeding stocks being greatly reduced while those in the reserve have remained relatively stable. The wetland areas in the reserve provide refuge for fish, some of which migrate upstream during flooding. The reserve thus plays a valuable social role by acting as a reservoir to replenish fish stocks and securing the breeding stock for the entire floodplain.