The town started in the 1880s as a saloon and water-refilling station for the Denver and Rio Grande Western Railroad.

Nearby cattle ranchers and sheep herders in the Book Cliffs north of town began using Cisco as a livestock and provisioning center.

[3] The ghost town's easy access and proximity to the freeway have lured vandals, heavily damaging the historical artifacts.

The town was also used in filming the opening and ending scenes of the 1971 cult classic movie Vanishing Point.

During the summer months, whitewater river rafters use Cisco as a landing site, particularly for a trip through Westwater Canyon.