There is a wide variety of animal and bird life seen at Samburu National Reserve. Several large game species common to Kenya's northern plains can be found in abundance here, including the following dry-country fauna: gerenuk, Grevy's zebra, oryx and reticulated giraffe. All three big cats, the lion, cheetah and African leopard can also be found here, as well as the elephant, Cape buffalo and hippopotamus.

Other mammals frequently seen in the park include olive baboon, warthogs, Grant's gazelle, Kirk's dik-dik, impala, and waterbuck. A black rhinoceros population has been re-introduced into the park after an absence of 25 years due to heavy poaching.

There are over 350 species of bird. These include grey-headed kingfisher, sunbirds, bee-eaters, Marabou stork, tawny eagle, Verreaux's eagle, bateleur, vulturine guineafowl, yellow-necked spurfowl, lilac-breasted roller, secretary bird, superb starling, northern red-billed hornbill, yellow-billed hornbill, and various vultures including the palm-nut vulture. The Ewaso Ng'iro river contains large numbers of Nile crocodile basks. Since 2005, the protected area is considered part of a Lion Conservation Unit.