The Niger River crosses the region, and is joined by the Bani, an important tributary, at the city of Mopti.

The region is separated into several areas: the Inland Niger Delta around Mopti, the Bandiagara cliffs and the plain of Bankass along the Burkina Faso frontier.

An airport at Mopti provides air service for the region, while the Niger River provides transportation to Koulikoro and Ségou to the west and Tombouctou and Gao to the east.

Though Mopti's location, once a Bozo village named Sanga, had long been inhabited, rapid expansion began under Seku Amadu's Massina Empire around 1820.

Expansion continued under the Toucouleur Empire of El Hadj Umar Tall as well as the French colonial administration.