As the secession crisis moved toward civil war in early 1861, Lieutenant Worden was sent to Pensacola with secret instructions for the local Naval commander. While returning to Washington, D.C., by rail he was arrested by Southern authorities and held as a prisoner of war for several months, an experience that badly damaged his health. In February 1862, upon resuming active duty, he was given command of the revolutionary ironclad Monitor and took her into a historic battle with CSS Virginia on 9 March 1862. Receiving serious eye injuries in the action, he had to relinquish command. The battle, however, made him a major war hero in the North.
While recovering, Worden was promoted to commander in July 1862. Further promoted to captain, he commanded the monitor Montauk during the first months of 1863, bombarding Fort McAllister, Georgia, in January, destroying the privateer Rattlesnake in February and participating in the 7 April 1863 attack on Fort Sumter. Captain Worden spent the remainder of the Civil War on the important duty of supervising the construction of new ironclads.
Following the end of the great conflict, Worden commanded USS Pensacola in the Pacific. He received the rank of commodore in 1868 and the next year began five years as Superintendant of the U.S. Naval Academy, during which time he was promoted to rear admiral. In 1875–77, Worden commanded the European Squadron. He then had shore duty until retiring from active duty in late 1886.
Rear Admiral Worden died at Washington, D.C., on 18 October 1897.