St. Louis called at Port Castries, Bahia, Rio de Janeiro, Montevideo, Punta Arenas, Valparaíso, Callao, and Acapulco before arriving at San Diego on 31 August 1907.

Operating off the west coast into the spring of 1908, she steamed from Puget Sound to Honolulu in June, then cruised in Central American waters from July to October.

From 14 July 1912 until 26 April 1913, she operated in support of the Oregon Naval Militia, then returned to the Puget Sound Navy Yard to be placed in the Pacific Reserve Fleet for a year.

Returning to Boston for repairs on 19 July 1917, she had completed six additional voyages, escorting convoys bound from New York for ports in Britain and France by the end of the war.

She disembarked military passengers at Sheerness on 26 September, then continued on to the Mediterranean and reported to the Commander, United States Naval Forces in Turkish Waters at Constantinople on 19 October.

The following day, her crew formed boat landing parties to distribute food among refugees quartered aboard naval transports anchored in the Bosphorus.

St. Louis continued her humanitarian duties at Constantinople and at Anatolian ports during the time of unrest caused by the Russian Civil War and the Turkish revolution.