Depredation can broadly affect marine socio-ecological systems, yet it has been little studied via modelling approaches. Here we used qualitative mathematical modelling of system feedback (Puccia and Levins’ loop analysis) and a system of ordinary differential equations to represent major interactions between a fishery, an exploited stock and a depredating species. We then assess response of depredation-impacted fisheries to three scenarios of sustained changes: i) increased fishing effort, ii) increased abundance of depredating species and iii) increased abundance of the exploited stock. Persistence of depredation-impacted fisheries depends on (1) the fishers’ success in retrieving fish onboard being relatively greater than the ability of depredating species to remove the catch from the gear and (2) sustainable management of the exploited and depredated stock. Moreover, predicted responses of depredation-impacted systems can be summarised according to four broad categories, which partially depend on (1) the population dynamics of the stock and its exploitation status, and (2) the ecology of the depredating species and the magnitude of its competition with fishers. In all categories, an increase in the rate of growth of the depredating species reduces fishery yield, which is likely to intensify fishing effort as fishers try and compensate for losses. However, such an increase in effort is only sustainable for well-managed stocks harvested by a fishery that is sufficiently profitable to support extra costs. We identify several processes that determine the co-existence of fishers, exploited stocks and depredating species and propose a suite of recommendations to better represent depredation in marine ecosystem and fisheries models.