[1] Still commonly referred to as Yorktown, she was assigned to a position near Mulberry Island in the James River to protect the right flank of the Confederate Army of the Peninsula.

On 13 September 1861 and again on 2 December, Commander Tucker took Patrick Henry down the river to a point about 1.5 miles (2.4 kilometers) above Newport News, Virginia, and opened fire on the Federal squadron at long range hoping to draw out some of the gunboats.

During the Battle of Hampton Roads on 8 March 1862 in which CSS Virginia destroyed the Federal warships USS Cumberland and USS Congress, Patrick Henry attempted to take the latter's surrender but was fired upon by shore batteries, and took a shell in her steam chest that killed four men.

In a daring night operation on 5 May 1862, she helped remove Confederate property from the Norfolk Navy Yard before it was abandoned to the Federals.

In October 1863, Patrick Henry housed the floating Confederate States Naval Academy at Drewry's Bluff, where instruction for 52 midshipmen began under the superintendency of Lieutenant William Harwar Parker.