A three-dimensional ecohydrodynamic model of Lake Ladoga based on the St. Petersburg Baltic Eutrophication Model (SPBEM) is proposed. Unlike existing models of the Lake Ladoga ecosystem, the proposed model is implemented on a high-resolution spherical grid (horizontal grid size ≈1 km), contains a benthic layer module and describes the cycles of nitrogen and phosphorus in the water column and bottom sediments. A run of the seasonal and interannual variability of the state of Lake Ladoga in the period 1979–2018 was carried out when setting as forcing the atmospheric influence and runoff of rivers flowing into Lake Ladoga for the hydrothermodynamic module and the supply of nutrients from the atmosphere and from land for the biogeochemical module. A comparison of the results of calculating the current climatic state of Lake Ladoga with the available satellite andexpeditionary observation data showed that the model correctly reproduces the climatic seasonal variation of the surface temperature field, its vertical distribution, average values and range of changes in the main characteristics of the lake’s ecosystem. The proposed model can be used to study the influence of external natural and anthropogenic factors on biogeochemical processes and the functioning of the Lake Ladoga ecosystem.