Regarded as one of the most promising officers in the Navy, he commanded several ships of the Mississippi Squadron during the Civil War under Flag Officer Foote, displaying outstanding initiative, energy and dash.
After the fall of Fort Henry, Gwin swept with his wooden gunboats up the Tennessee River all the way to regions of Alabama, spreading destruction and terror. This action was a major factor in the collapse of the Confederate lines far behind him in Kentucky. Fire support from two of his gunboats, Tyler and Lexington, helped save Union troops from disaster at the Battle of Shiloh, bringing high praise from General Grant.
Lt. Commander Gwin was wounded in action 27 December 1862 while commanding gunboat Benton at the Battle of Haines Bluff on the Yazoo River. He died from these injuries 3 January 1863 on board a hospital ship in the Mississippi River.