Before the arrival of the Spanish explorers, the area of South San Diego was inhabited by the Kumeyaay people.

John J. Montgomery achieved the first controlled flight with a heavier-than-air flying machine in the United States when he successfully flew three glider aircraft designed in the period 1883-1886 from Otay Mesa.

A monument to his historic flights is known as Silver Wing Park, located on Coronado Avenue, just east of Beyer Boulevard.

Brown Field Municipal Airport is located in the Otay Mesa region of South San Diego.

[7] The City of San Diego groups these neighborhoods into larger sections for planning purposes.

South San Diego is served by the Sweetwater Union High School District.