Quantifying age, rate, and lateral variation of deformation and exhumation in convergent systems relies on integration of geologic map patterns, ag, and locations of reset thermochronometer systems, and synorogenic sediment distribution. The central Bolivian Andes provide an ideal location to examine the influence of variations in shortening and stratigraphic architecture on the structural evolution of the mountain range due to differential age and rates of shortening and distinct sedimentary basin geometries along strike. To quantify age and rate of shortening, we link thermokinematic modelling of sequentially deformed, forward-modelled, balanced cross-sections to synorogenic and thermochronologic histories. The preserved basin history in the Altiplano and Eastern Cordillera argues for an early fold-and-thrust belt located in the now-Western Cordillera, with subsequent propagation of shortening eastward around 40–50 Ma. Flexural modelling incorporating isostasy and erosion requires multiple basement thrust sheets with 35–97 km of displacement. A temporally evolving effective elastic thickness, as well as imposed subsidence in the foreland and uplift in the hinterland, is required to reproduce the surface geology, increase Subandean foreland basin depth, limit Altiplano sedimentation, and facilitate Altiplano uplift to modern elevation. Thermokinematic modelling is compatible with initiation of deformation at 50–40 Ma in a marked increase in Subandean velocities from ~5.5 to 8–10 mm/yr from ~12–10 Ma to present. Out-of-sequence thrusting at the westernmost limit of the Subandes is required to match measured young and partially reset zircon helium ages. Out-of-sequence faulting is supported by high Ksn values, indicative of active uplift, and was likely promoted by the abrupt eastern edge of the Paleozoic basin rocks, which limited forward propagation of structures, and/or increased erosion due to focused precipitation. Our results highlight the importance of incorporating detailed structural modelling in differentiating the geometry, kinematics, and timing of deformation to reproduce thermochronologic ages and basin histories.