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San Lorenzo High first opened in 1950, and the first graduating class was in 1953. The school is located on the former site of an apricot field, and was the second school in the Hayward area, following only Hayward High.

When it first opened, SLz was a part of the Hayward school district. However, in 1963, under pressure from the state of California to unify into smaller school districts, San Lorenzo became part of the new San Lorenzo Unified School District.