The reason for the huge diversity of fauna and flora is the great variety of different ecosystems on the park, ranging from coral reefs and sandy beaches to subtropical dune forests, savannas, and wetlands. Animals occurring on the park include elephant, leopard, black and white rhino, buffalo, and in the ocean, whales, dolphins, and marine turtles including the leatherback and loggerhead turtle. The park is also home to 1,200  Nile crocodiles and 800 hippopotami. In December 2013, after 44 years of absence, lions were reintroduced to iSimangaliso

There are large outcroppings of underwater reefs which are home to brightly coloured fish and corals. Some of the most spectacular coral diversity in the world is located in  Sodwana Bay. The reefs are inhabited by colour-changing octopuses and squid ready to ambush unsuspecting prey. Occasionally gigantic whale sharks can be seen gliding through the water, mouth agape to scoop up tiny plankton.Twenty-four species of bivalve molluscs are recorded in St. Lucia Lake, which constitutes a considerable portion of the park.