The ocean is affected by multiple anthropogenic stressors including climate change, the effects of which are already evident in many ocean ecosystems. The ABACuS v2 end-to-end model together with climate projections from the NEMO-MEDUSA 2.0 model were used to evaluate the effects of fishing, warming and horizontal and vertical mixing on the southern Benguela upwelling system. Of the drivers examined in this study, warming had the greatest effect on species biomass, with mainly negative effects. The magnitude of the impacts of warming intensified from the RCP 2.6 to the 8.5 emission scenario. Fishing negatively affected demersal and large pelagic fish, which in turn resulted in a biomass increase of forage fish due to a decrease in predation pressure. Water mixing was found to have minor indirect effects on zooplankton biomass and fish. The responses of species and species groups to the combined effects of fishing and warming were approximately equally divided between additive, synergistic and antagonistic. Interpretation of our model results suggests that the southern Benguela system is likely to be affected by climate change, including substantial changes in the abundance of some species important to the region's fisheries. Future planning for fisheries needs to take this into account, including through management that strives to maintain the resilience of key species and the system as a whole. In line with previous studies on the southern Benguela, the results reinforce the importance of including consideration of the indirect and combined impacts of climate change and fishing in management and planning.