Planning for what would become SR 125 north of I-8 began in 1954. Route 282 was defined as a route from Brown Field through La Mesa extending to Route 277 in 1959, and in 1961 the latter terminus was changed to Route 278. The California Highway Commission selected a route for the highway in mid-1963. In the 1964 state highway renumbering, SR 125 was designated as the highway from SR 75 near Brown Field to SR 56. Route 198 was renumbered as State Route 67; the portion south of I-8 was renumbered as SR 125.