[5][6] For the 200 years leading up to 1875, nomadic Indian tribes representing the Apache, Comanche, Kiowa, and others roamed the Panhandle following the huge bison (buffalo) herds.

In search for an alternate route to California through Santa Fe, New Mexico, Josiah Gregg (1840), and Captain Randolph B. Marcy (1845) surveyed trails that crossed Hemphill County, following the south bank of the Canadian River.

In 1886, the Southern Kansas Railway Company, a Santa Fe subsidiary, began to build a rail line into the Panhandle of Texas.

The tracks entered Hemphill County during 1887 and further encouraged settlement in the area, creating three town sites: Mendota, Canadian, and Glazier.

In 1907, Canadian was designated a division point by the Santa Fe, a factor which brought diversification to the previously ranching economy of the area.

Though oil was discovered in the county in 1955, production remained relatively small because the technology had not yet progressed to efficiently capture the very deep reserves known to exist.

In 2000, about 505,000 bbl (80,300 m3) of oil and more than 8 billion cubic feet of natural gas were produced in the county, but the future looked very bright.

From 1952, Republicans have held sway, losing the county only in the 1964 landslide by native son Lyndon Johnson.