The brigade originally formed under orders from Major General Thomas C. Hindman following a successful recruiting expedition into Missouri by Joseph O. Shelby, John T. Coffee, and Upton Hays, who each recruited a regiment. These new regiments were brigaded under the command of Colonel Shelby. The brigade participated in four major raids into Missouri during the war, earning a repuation as the most formidable brigade in the theater.
Shelby was promoted to brigadier general following his successful raid of 1863. When Shelby later assumed division command, he was replaced by M. Jeff Thompson. The brigade remained in Shelby's Division in the Army of Missouri and fought in Maj. Gen. Sterling Price's Missouri Expedition in 1864—saving Price's army from destruction several times, including the retreat at the Battle of Marmiton River. 
In the autumn of 1864, some 1,500 of Shelby’s Iron Brigade cavalry surrounded Sedalia, Missouri, and overpowered local Union militia defenders. They began to loot and sack the town on October 15, 1864. Once General Thompson arrived in Sedalia, he ordered his men to stop the destruction, and moved them on, leaving Sedalia once again in Union hands.
Rather than surrender in 1865 with the collapse of the Confederacy, in June, Shelby and his men rode south into Mexico to offer their services to Emperor Maximilian, who declined to accept the ex-Confederates into his armed forces. However, the emperor did grant them land for an American colony in Mexico, and many of Shelby's Iron Brigade settled on the free land.
- Buresh, Lumir F., October 25th and the Battle of Mine Creek, The Lowell Press, 1977.
- Edwards, John N., Shelby and His Men, Cincinnati: Miami Printing and Publishing Co., 1867.
- Mueller, D.L., M. Jeff Thompson: Missouri’s Swamp Fox of the Confederacy, University of Missouri Press, 2007. ISBN 0-82621-724-9.
- Edwards, p. 78.
- Buresh, pp. 166-182.
- From Sedalia: It's Late Defence and Capture (Missouri Democrat, ? October 1864)
- Mueller, (2007), pp.85-86.
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