In 1869 the Nebraska legislature authorized the construction of a facility to care for mentally ill persons. The 160-acre site was located just north of the village of Yankee Hill, and southwest of Lincoln, the newly established state capital. Through this area ran the Nebraska City-Fort Kearny Cutoff, a wagon road used in the 1860s to transport freight from the Missouri River to military posts and settlements in the Platte Valley.
The Nebraska Hospital for the Insane, opened in December 1870, was destroyed by fire the following April. A new building was completed in 1872. The name of this facility was changed to the Lincoln State Hospital in 1921 and to the Lincoln Regional Center in 1969. From an initial total of less than 50, the number of patients has varied as methods of diagnosis and treatment of mental illness have changed. In 1955 the patient census was 1750. By the 1980s, with modern medicines and an emphasis on outpatient care, the hospital had fewer than 250 residents.