Abstract Intensive, large‐scale agriculture promotes the conversion of natural habitats and diversified crops into monocultures, decreasing both native vegetation cover and landscape heterogeneity, leading to landscape simplification. Yet, a key knowledge gap persists on the relative impacts of the loss of native vegetation and landscape heterogeneity on biodiversity. Addressing this gap is pressing to support policies that conciliate agricultural production and biodiversity conservation and to move forward some scientific controversies, as the ‘land sharing versus land sparing’ and ‘habitat loss versus fragmentation’ debates. Through a hierarchical sampling design that maximised variation, while minimising correlation, between landscape heterogeneity and native vegetation cover, we recorded the occurrence of medium and large‐bodied mammals in native vegetation and agricultural areas of 55 landscapes in a global conservation hotspot and a key commodity production area—the Brazilian Savanna, Cerrado. We compared simple, additive and interactive models to investigate the effects of landscape heterogeneity and native vegetation cover on richness and composition of native and invasive mammals. Native and invasive mammal communities were affected by both native vegetation cover and landscape heterogeneity, although the effects of the first was stronger than the later. Both aspects had positive effects on native species richness and negative effects on invasive species richness, indicating that the loss of native vegetation and the reduction in landscape heterogeneity lead to biotic homogenisation. Yet, while landscape heterogeneity benefited most native species, the direction of its effect varied among invasive species and depended on native vegetation cover. Synthesis and applications. Besides reducing habitat loss, avoiding landscape homogenisation is key for conciliating agricultural production and biodiversity conservation, pointing to the relevance of policies encouraging crop diversification. As increasing landscape heterogeneity can in part compensate the negative effects of losing native habitat on biodiversity in agroecosystems, policies can gain feasibility by adjusting the balance between native vegetation cover and landscape heterogeneity according to what best suits local restraints and demands.

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