The relationship between ecosystem disturbance and biodiversity levels has been a central focus of ecological research for the past half-century. The intermediate disturbance hypothesis, which suggests that maximum biodiversity is achieved through the coexistence of early and late successional species, however, has been challenged for its lack of clarity regarding the intensity, duration and extent of disturbances. This Perspective article advocates for a broader biocultural framework to move from the notion of disturbance to an understanding of human–environment mediations. Our proposed biocultural hypothesis acknowledges that, in certain cultural contexts, interventions by Homo sapiens at different environmental scales – mainly at the landscape level – can generate peaks in beta and gamma biodiversity compared to reference ecosystems. We illustrate these human–environment mediations through studies conducted in the biocultural region of Mesoamerica and comparative research findings, particularly from the Amazon Basin and West and Central Africa. In our conclusions, we discuss the need to establish collaborative research programmes around the proposed biocultural hypothesis, addressing management and institutional actions that will strengthen the engagement of Indigenous people and rural local communities with their historical territories that we name ‘Priority Biocultural Areas’.