 Via the Des Moines River, it is part of the watershed of the Mississippi River.The Middle River rises in southwestern Guthrie County and initially flows southeastwardly through Adair County, then eastwardly through Madison County, then east-northeastwardly through Warren County, passing the towns of Casey, Winterset, Patterson, Bevington, Martensdale, Spring Hill and Carlisle.A substantial portion of the Middle River's course through Warren County has been straightened and channelized.