Mesozooplankton can be considered the most important secondary producers in marine food webs because they hold an intermediate position between the phytoplankton assemblage and the upper trophic levels. They also are a robust indicator of climatic and hydrological conditions. We conducted an analysis of the interannual variability of the spring mesozooplankton assemblage, as sampled by the PELGAS fisheries survey in the southern part of the Bay of Biscay (Northeast Atlantic Ocean) between 2003 and 2013. We examined hydrology and trophic drivers to explain the variability. Our results revealed that the subsurface temperature, the subsurface salinity, the biomasses of subsurface pico-, nano-, and microphytoplankton, and the copepod assemblage exhibited a recurrent spatial pattern that was driven mainly by freshwater and nutrient inputs from the main rivers. The mesozooplankton assemblage was dominated by copepods (82%), composed of coastal, neritic, and oceanic copepod genera that paralleled the various hydrological fronts converging in the southern Bay of Biscay. The copepod community displayed high temporal-variability; there were three periods of abundant adult copepods throughout the southern Bay of Biscay. The copepod community was structured primarily around the drive for resource control, especially by the microphytoplankton biomass (24.3% of the total variability), and to a lesser extent by hydrological features (13.7% of the total variability).