The Masai Mara is perhaps most famous for its lions. All other members of the "Big Five" are to be found in the Masai Mara, although the population of black rhinoceros is severely threatened, with a population of only 37 recorded in 2000. Hippopotami are found in large groups in the Masai Mara and Talek Rivers. Cheetahs are also to be found, although their numbers are also threatened, chiefly due to tourist disruption of their day-time hunting. As mentioned above, the plains between the Mara river and the Esoit Oloololo Escarpment are probably the best area for game viewing, in particular regarding lion and cheetah.

Like in the Serengeti, the wildebeest are the dominant inhabitant of the Masai Mara, and their numbers are estimated in the millions. Around July of each year these ungainly animals migrate in a vast ensemble north from the Serengeti plains in search of fresh pasture, and return to the south around October. The Great Migration is one of the most impressive natural events worldwide, involving an immensity of herbivores: some 1,300,000 Wildebeest, 360,000 Thomson's gazelle, and 191,000 Zebra. These numerous migrants are followed along their annual, circular route by a block of hungry predators, most notably lions and hyena.

Numerous other antelope can be found, including Thomson's and Grant's gazelle, impala, topi and Coke's hartebeest. Large herds of zebra are found through the reserve. The plains are also home to the distinctive Masai giraffe as well as the common giraffe. The large Roan antelope and the nocturnal bat-eared fox, rarely present elsewhere in Kenya, can be seen within the reserve borders. The Masai Mara is a major research centre for the spotted hyena. Additionally, over 450 species of birdlife have been identified in the park, including vulture, marabou, and secretary bird, hornbill, crowned crane, ostrich, long-crested eagle, and pygmy falcon.