Upper plates of subduction zones commonly respond to flat slab subduction by structural reactivation, magmatic arc disruption, and foreland basin inversion. However, the role of active strike-slip faults in focusing convergent deformation and magmatism in response to oblique flat slab subduction remains less clear. Here, we present new detrital apatite fission-track (dAFT) ages from 12 modern catchments in the eastern Alaska Range, Alaska, USA, to reveal how the dextral Denali fault system has facilitated bedrock exhumation and topographic growth during ca. 30 Ma-to-present oblique flat slab subduction of the Yakutat oceanic plateau. Additionally, a 940 ka (⁴⁰Ar/³⁹Ar whole rock) basalt flow is spatially associated with Cenozoic structures, locally reset AFT ages and provides the first evidence for Quaternary volcanism along the southern flank of the eastern Alaska Range. We integrate our new data with other thermochronologic, geochronologic, and regional geologic datasets to show that (1) most high topography regions in southern Alaska have undergone rapid bedrock cooling and exhumation since ca. 30 Ma; (2) elevated terrain and young cooling are spatially associated with long-lived active strike-slip fault systems; (3) topographic growth associated with strike-slip fault deformation led to local inversion of basin systems and drainage reorganization; (4) the onset of oblique oceanic plateau subduction is coeval with a southward shift in arc magmatism from one region of active strike-slip faulting to another above the northeastern edge of the flat slab; and (5) Quaternary volcanism marks the revival of magmatism in the eastern Alaska Range above the geophysically imaged northeastern edge of the flat slab. Our analysis of the post-30 Ma geologic evolution of southern Alaska demonstrates that strike-slip fault systems that were active at the time of slab flattening evolved into transpression zones that focused bedrock cooling, rock exhumation, and topographic growth.