© 2018, Springer Nature B.V. Context: Understanding population responses to landscape structure is critical to improve landscape planning. Yet, large uncertainty remains about how such responses vary among regions with different disturbance intensity. This knowledge is particularly important for forest-specialist species, such as spider monkeys. Objectives: Assessing the effect of landscape composition and configuration on the abundance and reproductive success of spider monkeys (Ateles geoffroyi) in two fragmented rainforests with different land-use intensity. Methods: We calculated the encounter rate (relative abundance) and immature-to-female ratio (reproductive success) of spider monkeys in two Mexican rainforest regions (12 forest patches per region, ~ 1140 h of field observations), and assessed their responses to three landscape predictors (forest cover, matrix functionality, and forest patch density) considering the scale of effect in each region. Results: Spider monkeys showed different responses to landscape structure in each region. Encounter rate increased strongly with matrix functionality in the more disturbed region, and tended to be negatively impacted by patch density in the best-preserved region, but this latter association was weak. Forest cover was positively related to immature-to-female ratio in both regions, but such association was stronger in the best-preserved region. Conclusions: Our findings suggest that forest loss has stronger negative effects on spider monkeys than forest fragmentation, especially in best-preserved rainforests. Matrix composition is relatively more important in more disturbed regions, where monkeys may be pushed to use the matrix more frequently for feeding and/or traveling. Preventing forest loss and improving matrix quality should be a priority for the conservation of this endangered species.