We examine the role of preexisting crustal structure within the Peninsular Ranges batholith on determining the location of the San Jacinto fault zone by analysis of geophysical anomalies and initial strontium ratio data. A 1000-km-long boundary within the Peninsular Ranges batholith, separating relatively mafic, dense, and magnetic rocks of the western Peninsular Ranges batholith from the more felsic, less dense, and weakly magnetic rocks of the eastern Peninsular Ranges batholith, strikes north-northwest toward the San Jacinto fault zone. Modeling of the gravity and magnetic field anomalies caused by this boundary indicates that it extends to depths of at least 20 km. The anomalies do not cross the San Jacinto fault zone, but instead trend northwesterly and coincide with the fault zone. A 75-km-long gradient in initial strontium ratios (Sri) in the eastern Peninsular Ranges batholith coincides with the San Jacinto fault zone. Here rocks east of the fault are characterized by Sri greater than 0.706, indicating a source of largely continental crust, sedimentary materials, or different lithosphere. We argue that the physical property contrast produced by the Peninsular Ranges batholith boundary provided a mechanically favorable path for the San Jacinto fault zone, bypassing the San Gorgonio structural knot as slip was transferred from the San Andreas fault 1.0–1.5 Ma. Two historical M6.7 earthquakes may have nucleated along the Peninsular Ranges batholith discontinuity in San Jacinto Valley, suggesting that Peninsular Ranges batholith crustal structure may continue to affect how strain is accommodated along the San Jacinto fault zone.