Multi-use landscapes are now recognized for their value in supporting biodiversity and aiding species conservation, including charismatic megafauna. However, arid and semi-arid open-canopy human-use landscapes have faced multiple anthropogenic stressors over the past centuries and have received meagre conservation attention, especially in South and Southeast Asia. Colonial legacy of attributing open natural ecosystems (ONEs) as “degraded lands” and resultant policy interventions have irreversibly transformed these ecosystems for agriculture, infrastructure development and green energy initiatives. However, a growing body of evidence suggests that such ecosystems, even with low-intensity use, can provide habitats for globally threatened species and support their conservation. India, a country with megafauna inhabiting human-use areas, growing economic and climate aspirations and a colonial past, provides a model for understanding the role of arid and semi-arid multi-use landscapes in supporting populations of large-bodied wildlife. Using key informant interviews with pastoralists and single-season single-species occupancy modelling framework, we explored distribution of three species: striped hyena Hyaena hyaena, sloth bear Melursus ursinus, and blackbuck Antilope cervicapra in an agro-pastoral semi-arid landscape in India’s Deccan Peninsula. Hyena, sloth bear and blackbuck occupied 52%, 26% and 63% of the landscape, respectively, despite the absence of protected areas. Conservative estimates also suggest that Indian grey wolf (Canis lupus pallipes) was present in at least 76% of the landscape. ONEs favoured occupancy of hyena and sloth bear, while low-intensity agriculture supported blackbuck presence. Our results highlight the conservation potential of multi-use landscapes and challenge the prevailing narrative of mischaracterizing semi-arid open ecosystems as “wastelands”. We also demonstrate the value of incorporating indigenous knowledge to aid conservation research and practices. Under global change scenarios, misclassification and mismanagement of critical socio-ecological systems, such as ONEs of Deccan Peninsula, will not only directly threaten the populations of endangered species but also weaken the land sharing potential of regions.