After shakedown in Cuban waters, "Preble" was assigned special duty in Mexican waters, arriving Vera Cruz 13 June. During the following weeks she made three voyages to Galveston, Texas, to obtain medical supplies including serum to fight bubonic plague which had developed during the rebellion of the Sonora triumvirate. In August she returned north to join the Atlantic Fleet in East Coast and Caribbean exercises. In January 1921 the Atlantic and Pacific Fleets joined off the Panama Canal Zone and cruised to the west coast of South America. Separating on 23 February, the Atlantic Fleet steamed back to the Caribbean.