The Rupununi is home to  healthy populations of several species that are endangered elsewhere. These species include Jaguars, Giant River Otters, Black Caiman, Giant Anteaters, Giant River Turtles, giant Pimelodid catfish, and Arapaima.

The presence of these species and the relative ease with which they can be seen makes the Rupununi and important component of Guyana's ecotourism activities.

The high habitat diversity and the presence of Orinoco, Amazon, and Guiana Shield species leads to very high species richness in the Rupununi. There are over 400 species of fish, over 600 species of birds, and over 190 species of mammals found in the Rupununi.

The Rupununi includes over 750 depression and oxbow lakes and ponds. There are also mountain streams, gallery forests, forest islands, seasonally flooded savannah, black water flooded forest and white water flooded forest all set in a complex geology.

As one of the oldest inhabited areas in Guyana, the Rupununi also has a rich cultural and social history. Recent history has been dotted with economic ventures in Balata (rubber) harvesting and cattle ranching.