Predator-prey relationship maintains the dynamics and health of the Manas wildlife ecosystem, and any serious disturbance may cause either population explosions or crashes of any ungulate species, which is unnatural. The Manas ecosystem supports the tiger as the main predator, and the leopard, wild dog and clouded leopards as co-predators. These predators rank as such in the predation hierarchy and have a distinct niche of their own. This relationship is yet to achieve the balanced demographic status after a period of serious loss of the prey individuals of different species during the last decade of the political unrest.

After the devastation of wildlife populations, the natural revival of the populations took place with the help of protection measures; predators and prey started multiplying in the safer conditions. However, as observed in the results of 2010-11 scientific studies leopard numbers were higher than tiger numbers. This could be indicative of a relatively unhealthy ecosystem where the space of the natural top predator (the tiger) has been taken over by the more opportunistic and smaller predator species (leopards and wild dogs). This situation may be a cause of concern and steps need to be taken to improve the ecosystem balance.

Tigers, generally, prey upon large sized ungulates, and travel over a long distance in their home ranges, away from habitations. While tigers kill a wide range of ungulate species in the Core Zone, sometimes even an adult bison or a Rhesus macaque, or even a python with a freshly swallowed ungulate, the hog deer, and wild pig form the most of its annual consumption.

Leopards generally have smaller and almost stable home ranges close to habitations. There seems to be no competition between the tiger and leopard, and they follow the tactics of mutual avoidance. Leopards are, however, sometimes also known to operate close to the movements of tigers in the Core Zone. They generally kill small sized preys, including domestic dogs, goats and birds, though they prey on hog deer, wild pig and sambar as well. The kills of leopards are also sometimes usurped by tigers in the Core Zone. In Manas, after the devastation of the ethnic violence which reduced the wildlife populations to alarmingly less numbers, leopards opportunistically filled more space in the highest trophic level of the ecosystem, as is evident from the higher density of leopards from tigers.

Wild dogs in the Core Zone are more transients, and travel frequently in packs over large distances. Though their home ranges overlap with those of tigers and leopards, their presence is so fleeting that they seldom come into conflict with the other two predators. The average pack size of the wild dog in the protected area is 5-10 animals. They also kill large preys. The other lesser predators such as clouded leopards and jackals prey upon small herbivores, rodents and birds.

In this predator-prey relationship, the prey species also have their defence mechanism against the predators to avoid being killed. The defence may include alarm calls, large aggregations, and taking shelter in refuge covers etc.