The geodynamic forces acting during Jurassic-Cretaceous South Atlantic rifting provoked intense transformations in West Gondwana, such as the reactivation of ancient basement structures, voluminous magmatism and general uplift of the new continental margins. Low-temperature thermochronology records cooling associated with uplift syn- and post-breakup along the Brazilian margin, while further south, in Uruguay, mostly pre-breakup uplift is identified. Thermochronometry data are scarce in Uruguay, but previous studies suggest that basement cooling and exhumation preceded West Gondwana breakup by hundreds of millions of years. To improve our knowledge of Uruguay's thermotectonic evolution, in this study we present 19 apatite fission-track ages, 42 apatite and 40 zircon (Usingle bondTh)/He single crystal ages for the Uruguayan shield (UYS), from which we modeled 19 inverse thermal histories. Our results suggest that the UYS temperatures were below 200 °C since the early Paleozoic, and that cooling below 110 °C started during the Carboniferous, with continuous exhumation of the basement until Early Cretaceous. The onset of this long-term uplift is correlated with orogenesis and terrane accretions in the SW margin of West Gondwana during the Paleozoic. Lithosphere thinning and uplift preceding breakup contributed to the continuous Late Paleozoic to middle Mesozoic exhumation, until the voluminous volcanism of the Paraná-Etendeka Large Igneous Province (c. 133 Ma). This magmatic event, combined with the thermal influence of the Tristão da Cunha mantle plume and rift spreading, likely raised the basement geotherm during the Late Cretaceous. Models suggest a slight increase in temperatures of the UYS from Late Cretaceous until the Oligocene, when a final cooling to surface temperatures took place. Our findings corroborate a long and complex thermal history for Uruguay, with crustal uplift occurring essentially before West Gondwana breakup.