<p>The topographic history of an orogen results from the interactions of climate and tectonics, and it can be reconstructed from the sedimentary record of its peripheral basins. Previous tectonostratigraphic studies, including flexural models, and sparse stable oxygen and carbon isotope data from the South-Pyrenean foreland basin suggest that a major period of topographic growth occurred in the late Paleocene-early Eocene. To further test this hypothesis, we present a stack of 658 stable isotope measurements on whole-rock marine carbonate mudstone from a 4800-m-thick composite sedimentary succession which provides a 12 Ma continuous record of environmental conditions during the early to middle Eocene (54 to 42 Ma). From the base of this record (at 54 Ma), oxygen isotopes &#160;(<em>&#948;</em>¹⁸O values) show a faster decrease rate than the coeval global negative excursion associated with the Early Eocene Climatic Optimum (EECO). This local alteration of the global <em>&#948;</em>¹⁸O signal indicates that topographic growth during this period, associated with significant tectonic activity, perturbed the oxygen isotopic composition of foreland waters. Thus, our data suggest that significant topographic uplift of the Pyrenean orogen started from at least 54 Ma and continued until ca. 49 Ma, reaching the maximum elevations of 2000&#177;500m in this phase from previous isotope and flexural studies. In addition, our record shows that the long-term carbon stable isotope composition during this period remained relatively stable with no similarity to the global bell-shaped long-term trend of the EECO. This is consistent with the restricted physiography of the South-Pyrenean foreland basin, mainly influenced by local sedimentary and water inputs. Overall, the Pyrenean topographic growth from the Late Cretaceous to the Miocene displays several growth stages that seem to be primarily determined by episodes of an increased rate of tectonic plate convergence. The duration of these growth stages (several millions of years) is possible documentation of the response time of mountain ranges to tectonic perturbations. The results of this work, therefore, demonstrate that stable isotope measurements<em> </em>on whole-rock sediments in foreland basins can provide key information for tectono-climatic and topographic reconstructions of mountain ranges.</p>