Its original inhabitants decades earlier were Native Americans, more Cheyenne than other tribes at the time the western expansion of the U.S. arrived.

The first significant development and settlement occurred in 1887 when the Missouri Pacific Railroad came through from the east, on its way to Pueblo and Colorado's rich gold fields of "Pikes Peak Or Bust".

The county seat is in Ordway, a town established in 1890 that quickly became the economic hub of the area.

Other towns still existing along the Missouri Pacific Railroad's route are Sugar City, Crowley, and Olney Springs.

A few years later, developers brought a canal east from the Arkansas River, with ambitious plans to irrigate a million acres (4000 km2) in Kansas; instead, the canal petered out in Crowley County but did irrigate 57,000 acres (230 km2) along its length.

By the 1970s almost all the water rights were sold from what is now called the Twin Lakes Canal to the fast-growing cities of Colorado's Front Range corridor.

Crowley County also today hosts two prisons: the Arkansas Valley Correctional Facility in Ordway, and the Crowley County Correctional Facility in Olney Springs.

No Democratic presidential nominee has won Crowley County since Lyndon Johnson's 1964 landslide.

Before that time, the county largely followed the patterns of Colorado politics in general, from strongly Democratic during the William Jennings Bryan and Woodrow Wilson eras to Republican leaning from the time of Wendell Willkie onwards.