Brigadier General Nathaniel Lyon, who commanded the Federal forces at Wilson's Creek, was an 1841 graduate of the United States Military Academy and a veteran of the Seminole and Mexican Wars. He had also served at various posts on the frontier before being assigned to command the U. S. Arsenal in St. Louis in 1861.

An ardent Unionist and a strong supporter of Lincoln and the Republican Party, Lyon worked closely with Missouri Congressman Francis P. Blair, Jr., to prevent the state from seceding from the Union.

His death at Wilson's Creek at the age of 43 made him the first Union general to die in battle during the Civil War.