Many subduction margins that rim the Pacific Ocean contain complex records of Cenozoic slab-window volcanism combined with tectonic disruption of the continental margin. The series of slab windows that opened beneath California and Mexico starting about 28.5 Ma resulted from the death of a series of spreading ridge segments and led to piecewise destruction of a subduction regime. The timing and areal extent of the resultant slab-window volcanism provide constraints on models that depict the subsequent fragmentation and dispersal of the overlying continental margin. The initial Pioneer slab window thermally weakened the overlying western Transverse Ranges and California Borderlands region starting about 28.5 Ma. A second thermal pulse occurred in the same region starting about 19 Ma during growth of the Monterey slab window. This additional heating, combined with the capture of a partially subducted Monterey plate fragment by the Cocos plate, initiated the pulling apart and rotation of the adjacent continental margin. Similarly, the capture of Guadalupe and Magdalena plate fragments by the Pacific plate and initiation of the Guadalupe-Magdalena slab window about 12.5 Ma are coeval with Baja California pulling away from the Mexico continental margin, with the break along the Comondú arc, in crust already thermally weakened by about 10 My of volcanism. In coastal California, distributed crustal extension and subsidence accompanied the new transform plate boundary, and continued until the slab windows cooled and plate motion coalesced along a through-going system of strike-slip faults. The transform boundary continues to evolve, and forward modeling predicts an instability with the current configuration as a result of convergence between the Sierra Nevada and Peninsular Ranges batholiths, starting about 2 My in the future. The instability may be resolved by a shift in the locus of transform motion from the San Andreas fault to the eastern California shear zone, or by breaking off another fragment of the Mojave or southern Sierra Nevada crustal blocks and translating it northward.