AbstractLow‐angle detachment fault systems are important elements of oblique‐divergent plate boundaries, yet the role detachment faulting plays in the development of such boundaries is poorly understood. The West Salton Detachment Fault (WSDF) is a major low‐angle normal fault that formed coeval with localization of the Pacific‐North America plate boundary in the northern Salton Trough, CA. Apatite U‐Th/He thermochronometry (AHe; n = 29 samples) and thermal history modeling of samples from the Santa Rosa Mountains (SRM) reveal that initial exhumation along the WSDF began at circa 8 Ma, exhuming footwall material from depths of >2 to 3 km. An uplifted fossil (Miocene) helium partial retention zone is present in the eastern SRM, while a deeper crustal section has been exhumed along the Pleistocene high‐angle Santa Rosa Fault (SFR) to much higher elevations in the southwest SRM. Detachment‐related vertical exhumation rates in the SRM were ~0.15–0.36 km/Myr, with maximum fault slip rates of ~1.2–3.0 km/Myr. Miocene AHe isochrons across the SRM are consistent with northeast crustal tilting of the SRM block and suggest that the post‐WSDF vertical exhumation rate along the SRF was ~1.3 km/Myr. The timing of extension initiation in the Salton Trough suggests that clockwise rotation of relative plate motions that began at 8 Ma is associated with initiation of the southern San Andreas system. Pleistocene regional tectonic reorganization was contemporaneous with an abrupt transition from low‐ to high‐angle faulting and indicates that local fault geometry may at times exert a fundamental control on rock uplift rates along strike‐slip fault systems.