Sakuragichō is one of Japan's oldest stations. It opened on June 12, 1872, as the original Yokohama Station when the service between Shinagawa and Yokohama provisionally started. The station was renamed Sakuragichō Station on August 15, 1915, when the then-new and second Yokohama Station opened near Takashimachō Station. Yokohama Station would eventually be relocated again after the 1923 Great Kantō earthquake, to its third and current location.
Between March 31, 1932, and January 30, 2004, Sakuragichō Station was the terminus of the Tokyu Toyoko Line.