The 59th fought its first severe action at the Battle of Antietam, where it was part of the ill-fated advance of Maj. Gen. John Sedgwick’s division into the West Woods, near the Dunker Church.

In June, the command of the regiment changed dramatically after Colonel William Northedge resigned due to charges of corruption and drunkenness on duty.

The regiment occupied the same position on July 3 against the Pickett-Pettigrew-Trimble Assault, during which was wounded its young adjutant, Lieutenant William H. Pohlman.

The 59th fought with the Army of the Potomac through Grant's Overland Campaign, seeing significant action at the Wilderness, Spotsylvania, Cold Harbor, and Petersburg.

Redesignated as 59th New York Veteran Volunteer Infantry, it served until the end of the war at Appomattox and was mustered out under Colonel William A. Olmsted on June 30, 1865.