Land-cover change and ecosystem degradation may lead to biotic homogenization, yet our understanding of this phenomenon over large spatial scales and different biotic groups remains weak. We used a multi-taxa dataset from 335 sites and 36 heterogeneous landscapes in the Brazilian Amazon to examine the potential for landscape-scale processes to modulate the cumulative effects of local disturbances. Biotic homogenization was high in production areas but much less in disturbed and regenerating forests, where high levels of among-site and among-landscape β-diversity appeared to attenuate species loss at larger scales. We found consistently high levels of β-diversity among landscapes for all land cover classes, providing support for landscape-scale divergence in species composition. Our findings support concerns that β-diversity has been underestimated as a driver of biodiversity change and underscore the importance of maintaining a distributed network of reserves, including remaining areas of undisturbed primary forest, but also disturbed and regenerating forests, to conserve regional biota.