The park covers 14,750 square kilometres (5,700 sq mi)[7] of grassland plains, savanna, riverine forest, and woodlands. The park lies in northwestern Tanzania, bordered to the north by the Kenyan border, where it is continuous with the Maasai Mara National Reserve. To the southeast of the park is the Ngorongoro Conservation Area, to the southwest lies Maswa Game Reserve, to the west are the Ikorongo and Grumeti Game Reserves, and to the northeast and east lies the Loliondo Game Control Area. Together, these areas form the larger Serengeti ecosystem.

The park is usually described as divided into three regions-
Serengeti plains: the almost treeless grassland of the south is the most emblematic scenery of the park. This is where the wildebeest breed, as they remain in the plains from December to May. Other hoofed animals - zebra, gazelle, impala, hartebeest, topi, buffalo, waterbuck - also occur in huge numbers during the wet season. "Kopjes" are granite florations that are very common in the region, and they are great observation posts for predators, as well as a refuge for hyrax and pythons.

Western corridor: the black clay soil covers the savannah of this region. The Grumeti River and its gallery forests is home to Nile crocodiles, patas monkeys, hippopotamus, and martial eagles. The migration passes through from May to July.

Northern Serengeti: the landscape is dominated by open woodlands (predominantly Commiphora) and hills, ranging from Seronera in the south to the Mara River on the Kenyan border. Apart from the migratory wildebeest and zebra (which occur from July to August, and in November), this is the best place to find elephant, giraffe, and dik dik.

Human habitation is forbidden in the park with the exception of staff for the Tanzania National Parks Authority, researchers and staff of the Frankfurt Zoological Society, and staff of the various lodges, campsites and hotels. The main settlement is Seronera, which houses the majority of research staff and the park's main headquarters, including its primary airstrip.

In addition to the migration of ungulates, the park is well known for its healthy stock of other resident wildlife, particularly the "big five", named for the five most prized trophies taken by hunters:

Masai lion: the Serengeti is believed to hold the largest population of lions in Africa due in part to the abundance of prey species. More than 3,000 lions live in this ecosystem.
African leopard: these reclusive predators are commonly seen in the Seronera region but are present throughout the national park with the population at around 1,000.
African bush elephant: the herds have recovered successfully from population lows in the 1980s caused by poaching, numbering over 5,000 individuals,[8] and are largely located in the northern regions of the park.
Eastern black rhinoceros: mainly found around the kopjes in the centre of the park, very few individuals remain due to rampant poaching. Individuals from the Masai Mara Reserve cross the park border and enter Serengeti from the northern section at times.
African buffalo: still abundant and present in healthy numbers.

Apart from the vast herds of migratory and some resident wildebeest and zebra, the park is also densly packed with other plains game incluiding half a million Thomson's and Grant's gazelle, over 8,000 Masai giraffe, warthog, topi, eland, waterbuck, duiker, impala, klipspringer, roan antelope, bushbuck, lesser kudu, fringe-eared oryx and hartebeest.

Carnivores include about 4,000 spotted hyena, jackal, honey badger, striped hyena, serval, and the recently introduced East African wild dog. Apart from the safari staples olive baboon and vervet monkey, patas monkey are also seen in the gallery forests of the Grumeti River.

Serengeti National Park has also great ornithological interest, boasting about 500 bird species, including ostrich, secretary bird, kori bustards, crowned cranes, marabou storks, martial eagles, lovebirds, and many species of vultures.