Abstract The Indian subcontinent today houses about one-third of the global population and is one of the most vulnerable regions to future climate variability. This region has seen changes in civilizations, kingdoms and more recently political regimes, that were intricately linked to the changing environment over the mid–late Holocene. A comparative analysis of human–environment interaction within different regions at different time scales of the Quaternary is, however, lacking. In this paper we discuss the human–environment interactions taking case studies from two diverse time periods and geographically different regions from the Indian subcontinent. First, we review and analyse the role of environmental change in the evolution of Indus civilization on the northwestern Indian subcontinent during the mid–late Holocene and secondly, we discuss the role of both the anthropogenic activities and environmental change during the Anthropocene in shaping up the Bengal Delta. Overall, during the mid–late Holocene, Indus cultural transformations were driven by natural environmental changes, whereas the anthropogenic activities in the last few centuries have modified the Bengal deltaic landscape, which has intensified the impacts of natural disasters – in both cases a change in socio-political scenarios occurred. Such studies can be used as benchmarks to understand the future response of societies to environmental changes.