Climate variability has played a vital role in the expansion and collapse of human civilizations across the World since ancient times. The Indus Civilization in South Asia has been the focus of investigations to archaeologists, historians, and anthropologists. But little attention was paid earlier to the role of climate variability in shaping the course of this well-established urban civilization. In this paper, we have presented a review of literature to understand various factors that affected the evolution of this cultural enigma. We suggest that the climate change in the region was a major controlling factor in determining the fate of Indus civilization settlements. The transformation of hunter-gatherers into pastoral community between 7000 and 3200 B.C.E., the establishment of village habitations along the Indus River and its tributaries in the Early Harappan phase, urbanization and shifting towards Ghaggar-Hakra rivers in the Mature Harappan phase, and final displacement towards Ganga-Yamuna doab (interfluve) region as village culture were largely modulated by the changing strength of the Indian summer monsoon and amount of precipitation in the region.