Shakedown Cruise
Vesuvius sailed for New York shortly after commissioning and then joined the Fleet at Gardiner's Bay, New York, on 1 October 1890. She operated off the east coast with the North Atlantic Squadron into 1895. Highlights of this tour of duty included numerous port visits and participation in local observances of holidays and festivals, as well as gunnery practice and exercises. Experience showed that the ship's unique main battery had two major drawbacks: first, the range was too short; second, the method of aiming was crude and inaccurate.

Spanish–American War Service
Decommissioned on 25 April 1895 for major repairs, Vesuvius re-entered service on 12 January 1897 with Lieutenant Commander John E. Pillsbury in command. The ship got underway from Philadelphia Navy Yard, bound for Florida, and operated off the east coast through the spring of the following year, 1898. By this time, American relations with Spain were worsening. The American Fleet gathered in Florida waters, and Vesuvius hurried south from Newport, Rhode Island, and arrived at Key West, Florida, on 13 May. She remained there until 28 May, when she headed for blockade duty in Cuban coastal waters. Vesuvius performed special duties at the discretion of the Fleet Commander in Chief and served as a dispatch vessel between Cuba and Florida into July 1898.

On 13 June, Vesuvius conducted the first of eight shore bombardment missions against Santiago, Cuba. The cruiser stealthily closed the shore under cover of darkness, loosed a few rounds of her 15-inch dynamite charges, and then retired to sea. Psychologically, Vesuvius's bombardment caused great anxiety among the Spanish forces ashore, for her devastating shells came in without warning, unaccompanied by the roar of gunfire usually associated with a bombardment. Admiral Sampson wrote accordingly, that Vesuvius bombardments had "great effect." Although the dynamite guns were relatively quiet, detonation of their large high explosive shells sounded different from contemporary gunpowder-filled artillery shells; and soldiers observed the explosions "made holes like the cellar of a country house."