By February 1862 Confederate forces in Kentucky and Tennessee were falling back in disorder. Fort Henry on the Tennessee River and Fort Donelson on the Cumberland River fell to combined land and naval forces under Brigadier General Ulysses S. Grant and Flag Officer Andrew H. Foote. These losses necessitated the abandonment of the Rebel stronghold of Columbus, Kentucky. The entire upper Mississippi Valley lay open to Federal invasion. Toward that end, a new Union army under Major General John Pope began organizing at Commerce, Missouri.

Confederate Major General John P. McCown was sent to plug the breach by fortifying Island No. 10, a one-mile-long island positioned in a bend in the Mississippi River that straddled the boundaries of Tennessee, Missouri, and Kentucky. Pope's army had to be held in check long enough for the main Confederate force, under generals Albert Sidney Johnston and P. G. T. Beauregard, to concentrate and launch a counterattack against Grant's advancing army.

The ensuing campaign at Island No. 10 created the first extensive siege of the Civil War. The ultimate capture of the garrison resulted in a new army command for Pope in Virginia. As for the Confederates, the campaign pointed to a faulty western strategy. Simply to concede the rivers and their adjoining cities to the Federal navy was politically unacceptable. Garrison after garrison was captured, however, in the attempt to defend the rivers to the last extremity. Between February 1862 and July 1863 the Confederates lost 64,400 troops, some nine divisions, in defending the rivers. This strategy was a significant contributing factor for Confederate defeat in the West.