The region of Kayes is bordered to the north by Mauritania, to the west by Senegal, to the south by Guinea and to the east by the region of Koulikoro.
In 2009 the region has a population of 1,996,812 inhabitants. Ethnic groups of the area include Soninkés, Khassonkés, Malinkés, Dialonkés, and Fulas (French: Peuls; Fula: Fulɓe).
Several rivers cross the region: the
Baoulé, the Bafing, and the Bakoy which join at the town of Bafoulabé to form the Sénégal River. The Falls of Félou (15 km from Kayes), the Falls of Gouina (60 km to the south-east of Kayes on the Sénégal River), Talari Gorges,
Lake Magui and
Lake Doro are located in the region.
At the Guinean border, the climate is rather wet, but becomes Sudanian and later Sahelian to the north.
The largest cities in the region are Kayes, Kita, Bafoulabé, Nioro du Sahel, Diéma, Yélimané, Sadiola, and Kéniéba
The Bafing National Park and the Boucle du Baoulé National Park are located in the region.