The Little Popo Agie River runs through unincorporated portions of Fremont County Wyoming.

[3] During the 19th Century, areas along the river were the site of violent encounters between the U.S. Army and Native Americans.

On July 1, 1875, an army cavalry detachment documented killing two Native Americans near the river.

[5] Since at least the early 20th Century, some sections of the river have had problems with pollution thought to have come from industrial operations at nearby oil extraction sites.

This led to several lawsuits being filed for damages by locals using the river's water for irrigation against oil companies operating in the area.