Frequently, as she patrolled the river and escorted transports and supply ships, her guns engaged hit-and-run batteries and bands of riflemen.

After the Southern guns had set two of the transports on fire and damaged Key West with two rifle shots, the Union ships reluctantly retired downstream out-of-range.

On 2 November at Johnsonville, Tennessee, Key West assisted Tawah in recapturing transport Venus, taken along with Undine and Cheeseman by the Confederates there 30 October.

On 4 November Key West, Tawah, and Elfin were caught in a narrow, shallow section of the river near Johnsonville by a Confederate force under General Nathan B. Forrest.

After a vigorous action in which Key West was hit 19 times by rifled artillery, the three Union gunboats, riddled and almost out of ammunition, were set afire and scuttled.