At 1,240,000 square kilometres (479,000 sq mi), Mali is the world's 24th-largest country and is comparable in size to South Africa or Angola. Most of the country lies in the southern Sahara, which produces a hot, dust-laden Sudanian savanna zone. Mali is mostly flat, rising to rolling northern plains covered by sand. The Adrar des Ifoghas lies in the northeast.

Mali's territory encompasses three natural zones: the southern cultivated Sudanese zone, central semiarid Sahelian zone, and northern arid Saharan zone. The terrain is primarily savanna in the south and flat to rolling plains or high plateau (200–500 meters in elevation) in the north. There are rugged hills in the northeast, with elevations of up to 1,000 meters. Desert or semi-desert covers about 65 percent of the country’s area. The Niger River creates a large and fertile inland delta as it arcs northeast through Mali from Guinea before turning south and eventually emptying into the Gulf of Guinea.

The Niger (with 1,693 kilometers in Mali) and Senegal are Mali’s two largest rivers. The Niger is generally described as Mali’s lifeblood, a source of food, drinking water, irrigation, and transportation.

The country's lowest point is on the Senegal River (23 m) and its highest point is Hombori Tondo (1,155 m).