Fort Meade was established during the winter of 1878-79 by units of the 1st and 11th infantry and the reorganized 7th Cavalry. The mission of the 10 company post was to provide military protection against the resentful Sioux for the gold seekers and settlers who had invaded the region both before and after the Black Hills Treaty of 1877.

General Phil Sheridan, famed Civil War Cavalry leader, reportedly selected the picturesque site for the new post. He is said to have ridden horseback around what became the parade ground in the center of the 12 square mile military reservation, pointing with his saber to where he wanted each building to be constructed.

The new post replaced Camp J.C. Sturgis, established in July of 1878, about two miles northwest of nearby Bear Butte. It was first named Camp Ruhlen for Lt. George Ruhlen, 17th Infantry quartermaster officer who supervised the building of the post. It was subsequently renamed Fort Meade in honor of General George Meade of Civil War frame.Its strategic location at the mouth of the natural gap in the hogback ridge forming the outer rim of the Black Hills, on the main Indian trail to the favorite hunting grounds of the Sioux, and near the confluence of the heavily-traveled Bismarck, Fort Pierre and Sidney trails of the pioneers, enabled Fort Meade to play a major role in maintaining peace on the western Dakota Frontier.

The 7th Cavalry, re-formed after the disastrous Battle of the Little Big Horn in 1876, constituted the first permanent garrison of the post. Its commander, Colonel Samuel D Sturgis, was on of the founders of the nearby town that bears his name.

In June, 1879, the horse named Comanche, who survived the Battle of the Little Bighorn, was brought to Fort Meade by the Seventh Regiment. There he was kept like a prince until 1888, when he was taken to Fort Riley, Kansas. He died at Fort Riley a few years later and was buried with military honors. Shortly thereafter the horse's remains were sent to a taxidermist, and in the early 1900s Comanche was displayed at the Natural History Museum at the University of Kansas in Lawrence, KS. A restoration of the display was completed in 2005.

It was here, too, that the Star Spangled Banner first became the official music for the military retreat ceremony, long before in became the National Anthem. In 1892, the post commander Colonel Caleb H. Carlton, 8th Cavalry, began the custom of playing the "Star Spangled Banner" at military ceremonies and requested that all people rise and pay it proper respect long before it became the National Anthem.

Many celebrated frontier Army units saw service at Fort Meade, including the 4th Cavalry which was headquartered there for over 20 years. It outlived all other frontier posts of the Upper Missouri West, surviving as a military installation until 1944 when in became a Veterans Administration Hospital as it remains today. Fort Meade still serves as a training site for the South Dakota National Guard and an Army National Guard Officer Candidate School. It is also home of Fort Meade National Cemetery.