The Grand Island and Wyoming Central branch of the Burlington railroad came through this area in 1887 and built a siding here named Mullen after a railroad contractor. In 1888 Trefren and Gandy platted the village of Mullen. Hooker County, named for Civil War General Joseph Hooker, was established March 29, 1889, with Mullen as the county seat. A two-room courthouse was constructed the same year.
By 1900 Mullen had some forty buildings including a school, bank, depot, blacksmith shop, and stores. The village was incorporated in 1906, and the present courthouse was built in 1912. The old courthouse now houses the Hooker County Tribune, established in 1888.
The 1904 Kinkaid 640-acre Homestead Act spurred settlement, and county population peaked in 1920. Even 640-acre homesteads proved inadequate for agriculture and ranching in the Sand Hills, and drought and depression in the 1930s accelerated the trend to larger ranches and fewer people. Hooker County, with Mullen as its only town, is one of Nebraska's most productive cattle-raising regions. Mullen Public School District is one of the largest by area in the state.