This paper presents a new synthesis for the late Cenozoic tectonic, paleogeographic, and geomorphologic evolution of the southern Sierra Nevada and adjacent eastern San Joaquin Basin. The southern Sierra Nevada and San Joaquin Basin contrast sharply, with the former constituting high-relief basement exposures and the latter constituting a Neogene marine basin with superposed low-relief uplifts actively forming along its margins. Nevertheless, we show that Neogene basinal conditions extended continuously eastward across much of the southern Sierra Nevada, and that during late Neogene–Quaternary time, the intra-Sierran basinal deposits were uplifted and fluvially reworked into the San Joaquin Basin. Early Neogene normal-sense growth faulting was widespread and instrumental in forming sediment accommodation spaces across the entire basinal system. Upon erosion of the intra-Sierran basinal deposits, structural relief that formed on the basement surface by the growth faults emerged as topographic relief. Such “weathered out” fossil fault scarps control much of the modern southern Sierra landscape. This Neogene high-angle fault system followed major Late Cretaceous basement structures that penetrated the crust and that formed in conjunction with partial loss of the region’s underlying mantle lithosphere. This left the region highly prone to surface faulting, volcanism, and surface uplift and/or subsidence transients during subsequent tectonic regimes. The effects of the early Neogene passage of the Mendocino Triple Junction were amplified as a result of the disrupted state of the region’s basement. This entailed widespread high-angle normal faulting, convecting mantle-sourced volcanism, and epeirogenic transients that were instrumental in sediment dispersal, deposition, and reworking patterns. Subsequent phases of epeirogenic deformation forced additional sediment reworking episodes across the southern Sierra Nevada–eastern San Joaquin Basin region during the late Miocene break-off and west tilt of the Sierra Nevada microplate and the Pliocene–Quaternary loss of the region’s residual mantle lithosphere that was left intact from the Late Cretaceous tectonic regime. These late Cenozoic events have left the high local-relief southern Sierra basement denuded of its Neogene basinal cover and emergent immediately adjacent to the eastern San Joaquin Basin and its eastern marginal uplift zone