After commissioning, USS Wassuc proceeded south; touched at Norfolk, Virginia; and then sailed back northward to the Washington Navy Yard where she arrived on 4 June.

Two days after Christmas of 1941, Wassuc departed Tompkinsville, Staten Island, New York, bound for Yorktown, Virginia, to receive mine warfare instruction duties and further work under the auspices of BuOrd.

Wassuc spent the next two years operating in the 5th Naval District, primarily plying the waters of the Chesapeake Bay region and occasionally ranging as far north as the Washington Navy Yard and as far south as Cape Hatteras.

The U.S. Army held primary responsibility for defensive coastal minelaying, and submarines and aircraft were proving superbly capable of carrying mine warfare to enemy shores.

She continued her coastwise routine, ranging from Provincetown, Massachusetts, and Cape May, New Jersey, to New York and Norfolk, Virginia, as well as Solomons Island, through the end of World War II.