The Tonle Sap Lake (TSL) is a flood-pulse system. It is the largest natural lake in South-East Asia and constitutes one of the largest fisheries over the world, supporting the livelihood of million peoples. Nonetheless, the Mekong River Basin is changing rapidly due to accelerating water infrastructure development (hydropower, irrigation, flood control, and water supply) and climate change, bringing considerable modifications to the annual flood-pulse of the TSL. Such modifications are expected to have strong impacts on fish biodiversity and abundance. This paper aims to characterize the spatio-temporal variations of fish taxonomic composition and to highlights the underlying determinants of these variations. For this purpose, we used data collected from a community catch monitoring program conducted at six sites during 141 weeks, covering two full hydrological cycles. For each week, we estimated beta diversity as the total variance of the site-by-species community matrix and partitioned it into Local Contribution to Beta Diversity (LCBD) and Species Contribution to Beta Diversity (SCBD). We then performed multiple linear regressions to determine whether species richness, species abundances and water level explained the temporal variation in the contribution of site and species to beta diversity. Our results indicate strong temporal variation of beta diversity due to differential contributions of sites and species to the spatial variation of fish taxonomic composition. We further found that the direction, the shape and the relative effect of species richness, abundances and water level on temporal variation in LCBD and SCBD values greatly varied among sites, thus suggesting spatial variation in the processes leading to temporal variation in community composition. Overall, our results suggest that fish taxonomic composition is not homogeneously distributed over space and time and is likely to be impacted in the future if the flood-pulse dynamic of the system is altered by human activities.