Kayes Region is one of ten first level national subdivisions in Mali called Regions. It is the first administrative area of Mali and covers an area of 120,760 square kilometres or 46,630 square miles. Its capital is the town of Kayes. The province was historically part of the Ghana Empire and the Mali Empire.

Kayes is a city in western Mali on the Sénégal River with a population of 127,368 at the 2009 census. Kayes is the capital of the administrative region of the same name. The name "Kayes" comes from the Soninke word "karré", which describes a low humid place that floods in rainy season. The city is located 420 kilometres (260 mi) northwest of the capital Bamako.