The spatiotemporal changes of lake water resources objectively reflect not only the process of the water resources balance, but also the ecological environment changes in the lake area. In recent decades, climate changes and human activities have caused great impacts on the spatial distribution of the earth’s water resources and the spatiotemporal process of the surface water cycle, which has caused a series of ecological crises and environmental problems, such as the drying-up of inland lakes, the disappearance of the oasis, water shortage or flooding and water pollution. Therefore, monitoring and fully understanding the dynamic changes of lakes is of great scientific significance for grasping regional water balance, water resources management, and sustainable development of the ecological environment. In this study, we focus on using multi-source satellite data on the estimation of water volume and multi-timescale variations analysis for large scale lakes. This study combines the problems in the practical application of “African Water Action”, taking the largest lake in Africa, Lake Victoria, as the study area, and utilizes long-term serial multi-source satellite data of the past 15 years (2003–2017), including Moderate-resolution Imaging Spectroradiometer (MODIS), Jason-1/-2/-3 and Gravity Recovery and Climate Experiment (GRACE) to perform the comprehensive analysis on the water volume change estimation. Firstly, the satellite altimetry data of Jason-1/-2/-3 and MODIS imagery was used to calculate series of water level, and to extract series of water surface area, respectively. On this basis, a more accurate regression model between the area and water level variation (ΔH) was constructed. Then, the model between water volume variation (ΔV) and ΔH, derived from area-ΔH model, was applied to calculate the relative water volume of Lake Victoria. Meanwhile, terrestrial water storage (TWS) changes between 2003 and 2016, derived from GRACE data, were also used for a comparative verification of the ΔV results. The results show the long-term series change trends of ΔV and the TWS are the same. Finally, the multi-timescale analysis of water volume changes was carried out on different time scales, such as the inter-annual, inter-monthly, and variation period.