The prefecture is home to 622,222 people (as of 2020[update]) and covers an area of 70,916 km2 (27,381 sq mi).

Most Kyrgyz in China reside in Kizilsu; they make up a little over a quarter of the prefecture's population.

The name Kizilsu (also spelled Kezilesu, derived from Chinese pinyin[4][5]) refers to the Kezi River and means "red water" in the Kyrgyz language.

The establishment of the short-lived breakaway state was thanks in part to a political and military alliance between Uyghurs and Kyrgyz in western Xinjiang.

The Southern Xinjiang Administrative Office of the People's Republic of China established the Kizilsu Kyrgyz Autonomous Region on 14 July 1954.