Cities are complex social-ecological systems in which environmental quality and the health and well-being of people are intricately linked. While some of these connections are well established and may be positive or negative, others are constantly changing and being reshaped through social trends, environmental change, and shifting policy priorities. The pace of change is quickening as we have entered an unprecedented period of city building and re-building spurred by an increasing population, economic growth, and aging buildings and infrastructure. Climate change will have an increasing influence on the environmental quality and liveability of our cities, and our response and adaptation to new conditions will be critical for the future sustainability of cities. Geographic information science has much to offer in terms of providing spatial analytical perspectives, data, and technologies to understand complex problems of urban sustainability and options for early adaptation to climate change. One of the particularly important benefits of spatial information and spatial analytic approaches is their ability to integrate diverse datasets for real places. This facilitates multidisciplinary science and decision-making that can leverage different methodologies and promote collaboration amongst researchers and practitioners from diverse knowledge domains. Geographic approaches can also bridge research with practice and facilitate adaptive management approaches and a range of spatially specific interventions in the urban environment. This presentation expands on these ideas and provides examples of a range of basic and applied science questions being addressed by the CSIRO Climate Adaptation Flagship.