As the Civil War neared its end, Barton realized that there were many soldiers whose whereabouts were unknown. She understood the anguish that their families felt in not knowing if they were taken prisoner, badly wounded, or killed in action and buried on the battlefield. With the support of President Abraham Lincoln, she created the Office of Correspondence with Friends of the Missing Men of the United States Army at Camp Parole in Annapolis, Maryland. This would later become known as the Missing Soldiers Office.
With the help of her staff Barton compiled list of missing soldiers and had them published in newspapers and posted in public places, requesting information from anyone with knowledge of these men. Her own estimates of the scope of this work are as follows: "letters of inquiry, and those giving information received up to the end of the year 1868, amounted to 63,182. The printed circulars of advice issued in reply, 58,693. The letters written, to 41,855. The printed rolls distributed, to 99,057."
A key component in the search for missing soldiers was the discovery of a register of the dead from Andersonville Prison in Georgia. This list was secretly copied by Union soldier Dorence Atwater, who as a prisoner was responsible for recording the daily burials at the camp. With Atwater's help help, many of the graves at Andersonville where identified, and Barton used this information in her work in locating missing soldiers. She was given the honor of raising the flag over the newly-created Andersonville National Cemetery on August 17, 1865.