Clark County, Kansas, was established on February 26, 1867, from the territory of the former Peketon County, and named for Charles F. Clarke, a captain in the 6th Regiment Kansas Volunteer Cavalry during the American Civil War, though the final 'e' was later dropped.

[4] The opening of the Mount Jesus Trail, passing near a hill in the center of the county named Mount Jesus by the Custer expedition in 1868 on its way from Fort Dodge to Fort Supply, along with the onset of Texas cattle drives through the county, marked the beginning of American settlement in Clark County.

Settlement intensified with the establishment of a road ranch by John Glenn in 1874 near present-day Ashland, the beginning of weekly stagecoach service along the Mount Jesus Trail in 1875, and the opening of additional cattle ranches in 1876.

Efforts to create a Benedictine colony in the late 1870s near Mount Casino were abandoned after resistance from cattlemen and an Indian raid.

[4] Clark City hosted the first school and newspaper in the county, but both activities shifted to Ashland as the latter town grew, including by direct payments to Clark City residents to relocate.

29.60% of all households were made up of individuals, and 17.00% had someone living alone who was 65 years of age or older.

From 1944 on, it has become a Republican stronghold in presidential elections aside from 1964 when Lyndon B. Johnson won the county as part of his nationwide landslide victory.