Upper Takutu-Upper Esequibo is a region bordering the region of Potaro-Siparuni to the north, the region of East Berbice-Corentyne to the east and Brazil to the south and west. It contains the towns Aishalton, Lethem, Good Hope and Surama. It is also the largest region of Guyana. Sir John Noe was an English missionary there. The Rupununi savannah is located between the Rupununi River and the Brazilian border. The region is in the Zona de Reclamación by Venezuela.

The Kanuku and Kamoa highlands and the vast Rupununi savannahs make up the Upper Takutu-Upper Essequibo region. The forested Kanuku Mountains divide this Region in two. The north savannahs are about 2,000 square miles in area, and the south savannahs are 2,500 square miles.

The population lives in scattered Amerindian villages and land settlement schemes.

Because of the grassy savannahs, the Rupununi is considered to be 'cattle country'. Most of the cattle are farmed to produce beef, and a few are kept for milk. There are large ranches at Aishalton, Annai, Dadanawa and Karanambo. Much of the beef produced here is sold in neighbouring Brazil, because transportation to the other regions of Guyana, especially Region Four, is very expensive.

The people of this region also mine semiprecious stones among the foothills of the Kamoa Mountains and among the Marundi Mountains. A wide variety of craft is produced in many of the seventeen Amerindian villages, and sold mainly to Brazil.

In Region Nine, you can see the Giant River Otter, the Arapaima (the largest freshwater fish in the world) and the black Cayman.