After the outbreak of the American Civil War, Woodworth returned to the east coast and reentered the Navy on September 10, 1861, as an acting lieutenant. On January 13, 1862, he assumed command of , a former ferry boat converted to a steam gunboat. This vessel was assigned to the Mortar Flotilla raised by Comdr. David D. Porter to support Flag Officer David Farragut's conquest of New Orleans, Louisiana, and the lower Mississippi River. He assisted in the capture of Forts Jackson and St. Philip in April and participated in operations around Vicksburg, Mississippi, in June and July. Porter commended Woodworth for these services, and President Abraham Lincoln recommended him to Congress for special thanks. On September 29, 1862, at his own request, he was detached from command of "John P. Jackson" and allowed to return to the North. Later that autumn, he was assigned to the Mississippi Squadron and reported at Cairo, Illinois, for duty.