Changes in the hydrological regimes and ecosystems of lakes Ladoga and Onego were studied using in situ data and simulations of biogeochemical nutrient fluxes. A lake ecosystem model has been developed, representing the biogeochemical cycling matter by transport and transformation processes, taking into account the dynamics of nutrientsin bottom sediments. Diagnostic (1996–2015) and prognostic (2016–2040) assessments of possible changes in the hydrodynamic conditions and ecosystem of Ladoga Lake were carried out. The initial and boundary conditions for the numerical experiments were set according to field observations. The comparison of simulated and observed results showed a satisfactory match of the spatial-temporal dynamics of hydrophysical and biogeochemical characteristics. Possible changes in the hydrophysical processes, primary production, and biogeochemical nutrient fluxes in Lake Ladoga until 2040 under climate change scenario A1B are shown. The model can be used to study processes in the ecosystem and the biogeochemical cycles occurring in ecosystems of large stratified lakes under climate change and human impact.