When the American Civil War began in 1861, Foote was in command of the New York Navy Yard. On June 29, 1861, Foote was promoted to captain. From 1861 to 1862, Foote commanded the Mississippi River Squadron with distinction, organizing and leading the gunboat flotilla in many of the early battles of the Western Theater of the American Civil War. Even though Foote was an officer in the United States Navy, the Western Flotilla was under the jurisdiction of the Union Army. In early February 1862, now holding the rank of flag officer (equivalent to the modern commodore), he cooperated with General Ulysses S. Grant against Fort Henry on the Tennessee River. Despite heavy damage to one of the gunboats, Foote was able to quickly subdue the fort. When the Confederate garrison commander, Brig. Gen. Lloyd Tilghman, sent out a flag of truce asking the terms of surrender, Foote sent back a blunt reply, “No sir, your surrender will be unconditional!”