Macdonough failed to make the design speed of 30 knots (56 km/h; 35 mph) during trials, and along with her fellow Fore River-built destroyer Lawrence proved to have poor sea keeping.

After shakedown, Macdonough spent seven months as a training ship for midshipmen at the United States Naval Academy, Annapolis, Maryland.

Placed in full commission on 21 November 1908, Macdonough became the flagship of the 3rd Torpedo Flotilla and sailed for Pensacola, Florida.

In mid-June the ship departed New Orleans, Louisiana for Charleston where she joined the Destroyer Force, Atlantic Fleet.

Her name was struck from the Naval Vessel Register on 7 November 1919 and her hulk was sold to Henry A. Hitner's Sons Company for scrapping on 10 March 1920.