The Kiamichi River rises in southeastern Oklahoma in the Kiamichi Mountains in Le Flore County. It flows in a west-southwesterly direction until it reaches the Sardis Lake area where it turns to the southwest. It then bends south and east emptying into Hugo Lake. It exits the lake in a southeasterly manner and finally reaches its end at the Red River where it contributes to Raymond Gary State Park.

In addition to Le Flore county, the river passes through Pushmataha County and Choctaw County.