Continental rifts are commonly flanked by zones of high elevation, but the cause of uplift remains controversial. Proposed uplift mechanisms include active and induced asthenospheric upwelling, and isostatically driven lithospheric flexure. Discrimination between these hypotheses requires close constraint of the timing of rift flank uplift and crustal extension. Here, we focus on the well-preserved Neogene Gulf of California rift. The western rift margin is characterized by a prominent east-facing kilometer-scale escarpment, which bounds a west-tilted, topographically asymmetric rift flank. We exploit west-draining canyons incised into the rift flank to constrain the timing of uplift to between ca. 5.6 and 3.2 Ma using 40Ar/39Ar dating of lavas, which show cut-and-fill relationships to the canyons. Rift flank uplift closely followed the onset of slip on the principal fault of the Loreto rift segment at ca. 8–6 Ma, the age of which we obtain from apatite (U-Th)/He and fission-track thermochronologic analysis of rift escarpment exhumation. Uplift was therefore coeval with lithospheric rupture and the onset of oceanic spreading between ca. 6 and 3 Ma, but post-dates a proposed asthenospheric upwelling event by ∼8–10 Ma. The timing of uplift is inconsistent with either active or induced upwelling as uplift mechanisms, and we conclude that rift flank uplift was driven by the flexural response to lithospheric unloading.