Isogo is located in eastern Kanagawa Prefecture, and in the southeast corner of the city of Yokohama. The area is largely flatland, with scattered small hills. The Ward is bordered to the east by Tokyo Bay.
During the Edo period, area around present-day Isogo Ward was formerly part of the tenryō territory in Sagami Province controlled directly by the Tokugawa shogunate, but administered through various hatamoto. The area consisted of small fishing villages, noted primarily for their catch of Sea cucumber. After the Meiji Restoration, the area became part of Kuraki District in the new Kanagawa Prefecture. In the cadastral reform of April 1, 1889, the area was divided into numerous villages. On April 1, 1901, Negishi village was annexed by neighboring Yokohama. The remaining northern portions of the district were annexed in 1911 and 1927. On October 10, 1927, the 14 former towns and villages were re-organized as Isogo Ward within the city of Yokohama.
Isogo Ward annexed the remaining southern portions of Kuraki District (Kanazawa Town and Mutsuuraso Village) in October 1936. During World War II, Isogo was bombed twice: once on April 15, 1945, and again during the devastating Yokohama Air Raid of May 29, 1945, during which 692 houses were burned down. On May 15, 1948, Kanazawa Ward was separated from Isogo Ward. During the 1960s, the coastal areas of Isogo were converted into a massive chemical and petrochemical industrial zone through the extensive use of landfill, and the population of the area increased dramatically. The Isogo Ward offices relocated to their present location in June 1967.
Isogo is largely a regional commercial center and bedroom community for central Yokohama, Kawasaki and Tokyo. The coastal area is part of the Keihin heavy industrial zone, and has numerous chemical and petrochemical plants.