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On the northwest edge of the city of Sheridan is Fort Mackenzie, a hospital administered by the Veterans Administration. The hospital is situated on approximately 272 acres of land, which is a small parcel compared to the 6, 280 acres that once was the Fort Mackenzie military reservation. Within that acreage are approximately seventy buildings and structures, most of which are arranged in two north-south rows and along a fishhook-shaped avenue. Two-thirds of the buildings within the hospital grounds were constructed in the first decade of the twentieth century when Fort Mackenzie was a military post. These buildings served various functions such as administrative offices, living quarters, hospital wards, warehouses, and maintenance shops. They are constructed of red brick in the colonial style. The rest of the hospital structures, built after 1930 and during the years the post served as a Veterans Hospital are complimentary in style and construction materials to original fort buildings. Fort Mackenzie was converted from a military post to a veterans hospital in the early 1920s.

Fort Mackenzie was named for Ranald Slidel Mackenzie (1840-1889), veteran of the Civil War and the Indian Wars of the West and Southwest. As colonel of the Fourth Cavalry, Mackenzie took part in the Powder River Expedition of 1876. In November of that year, leading a mounted column during General George Crook's winter campaign against High Plains Indians, he surprised and defeated Chief Dull Knife's band of Northern Cheyenne near the edge of the Big Horn Mountains. Fort Mackenzie was established as a military base for the purpose of protection of white settlers in a Rocky Mountain-High Plains region home to Indians belonging to half a dozen different tribes. In September, 1898 Charles F. Manderson, a former senator from Nebraska, and others, informed the War Department of the need for a military post in the Northwest and recommended Sheridan, Wyoming as a site. In October, 1898 General E. V. Sumner, Commander of the Department of the Colorado and the Missouri, was directed by the War Department to investigate and report upon the matter of establishing a military force at Sheridan. In his report Sumner supported Manderson's claims and on December 14, 1898, the Secretary of War approved the report and authorized the expenditure of $12,000 for temporary buildings at Sheridan. Legislation was introduced which called for the establishment of a post near Sheridan and included a $100,000 appropriation. The bill was signed by President McKinley on April 7, 1900. The garrison was at its peak strength with 601 men in 1911. Fort Mackenzie's usefulness as a military post was at an end with the entry of the United States in World War I in 1917. The post was officially abandoned on November 3, 1918.

The fort was transferred from the War Department to the Public Health Service in March 1921. A year later it was transferred from that agency to the Veterans Bureau. In March 1922 President Harding signed a deficiency appropriation bill containing an item of $100,000 for use in converting the post to a hospital, and that spring the first patients began to arrive at Fort Mackenzie Veterans Hospital. When the hospital opened it had a bed capacity of 125 patients. At peak patient load just after World War II, the hospital contained 900 patients and was one of the largest neurophychiatric hospitals in the country. At the time of its nomination to the National Register of Historic Places, the hospital had an operating bed capacity of 364, a staff of 505 and a budget of $10,000,000.

The significance of Fort Mackenzie as a historic site derives from both its history and its architecture. Its history relates to two major functions: its function as a military post and as a veterans hospital. From 1898 to 1916 Fort Mackenzie was an army post, but it is not clearly understood what role it played in American military history. That it had an active role in the High Plains Indian Wars is doubtful, since fighting had ceased and Indians were located on reservations two decades before the post was established. Wyoming's congressional delegation tried to establish it as a regimental post, but that effort was likely inspired more by economic and political, rather than military reasons. The existence of the many buildings and structures at Fort Mackenzie affords physical evidence of the impact the fort has had upon the lives of those associated with the facility. The dozens of red-brick colonial style buildings form an impressive complex that is equaled or surpassed only by F. E. Warren Air Force Base in Cheyenne and Fort Yellowstone at Mammoth, as a homogeneous collection of historic federal buildings in the state.