It lies mostly in the American state of Colorado, draining land between the North and South Forks of the Republican River, and it flows into the North Fork in Nebraska after flowing a short distance through Kansas.

[4][7] From there, the river flows generally northeast across the High Plains in eastern Colorado.

It then crosses the extreme northwestern corner of Kansas before entering far southwestern Nebraska.

The Arikaree River has been made one of the designated areas under the Colorado Natural Areas Program because it is "part of the largest and best remaining example of a naturally functioning Great Plains river system in Colorado."

The area is a sanctuary for many bird species, including burrowing owls, ferruginous hawks, and greater prairie chickens.