Reconstructing the evolution of Earth’s landscape is a key to understanding its future evolution and to identifying the driving forces that shape Earth’s surface. Cosmogenic nuclide and thermochronological investigations are routinely used to quantify Earth surface processes over 102–104 yr and 106–107 yr, respectively. A comparison of the rates of surface processes derived from these methods is, however, hampered by the large difference in their time scales. River profiles bridge this time gap and record the regional uplift history over 102–107 yr. Here I present an integrative inverse modeling approach to simultaneously reconstruct river profiles, model thermochronological and cosmogenic nuclide data, and derive robust information about landscape evolution over thousands to millions of years. An efficient inversion routine is used to solve the forward problem and find the best uplift history and erosional parameters (such as the exponents of discharge [m] and slope [n] in the stream power equation) that reproduce the observed data. I test the performance of the algorithm by inverting a synthetic data set and a data set from the Sila massif (Italy). Results show that even complicated uplift histories can be reliably retrieved by the combined interpretation of river profiles and thermochronological and cosmogenic nuclide data.