The Pajaro River forms the southern boundary of Santa Cruz County and of the city of Watsonville, and is bordered by the Pajaro Valley. Since the river is also a county boundary, only the northern side of the river valley is in Santa Cruz County. The southern side is in Monterey County. Further inland, the river forms part of the boundary between San Benito County and Santa Clara County, originating near the county boundary where it crosses the southern Santa Clara Valley.
On the Santa Cruz County side, main tributaries are Watsonville Slough, Corralitos Creek, and Coward Creek.