Overexploitation of wildlife populations occurs across the humid tropics and is a significant threat to the long-term survival of large-bodied primates. To investigate the impacts of hunting on primates and ways to mitigate them, we developed a spatially explicit, individual-based model for a landscape that included hunted and un-hunted areas. We used the large-bodied neotropical red howler monkey (Alouatta seniculus) as our case study species because its life history characteristics make it vulnerable to hunting. We modeled the influence of different rates of harvest and proportions of landscape dedicated to un-hunted reserves on population persistence, population size, social dynamics, and hunting yields of red howler monkeys. In most scenarios, the un-hunted populations maintained a constant density regardless of hunting pressure elsewhere, and allowed the overall population to persist. Therefore, the overall population was quite resilient to extinction; only in scenarios without any un-hunted areas did the population go extinct. However, the total and hunted populations did experience large declines over 100 years under moderate and high hunting pressure. In addition, when reserve area decreased, population losses and losses per unit area increased disproportionately. Furthermore, hunting disrupted the social structure of troops. The number of male turnovers and infanticides increased in hunted populations, while birth rates decreased and exacerbated population losses due to hunting. Finally, our results indicated that when more than 55% of the landscape was harvested at high (30%) rates, hunting yields, as measured by kilograms of biomass, were less than those obtained from moderate harvest rates. Additionally, hunting yields, expressed as the number of individuals hunted/year/km², increased in proximity to un-hunted areas, and suggested that dispersal from un-hunted areas may have contributed to hunting sustainability. These results indicate that un-hunted areas serve to enhance hunting yields, population size, and population persistence in hunted landscapes. Therefore, spatial regulation of hunting via a reserve system may be an effective management strategy for sustainable hunting, and we recommend it because it may also be more feasible to implement than harvest quotas or restrictions on season length.