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Human experiences with nature are important for our culture, economy, and health. Anthropogenically-driven climate change is causing widespread shifts in biodiversity and resident urban wildlife are no exception. We modelled over 2,000 animal species to predict how climate change will impact terrestrial wildlife within 60 Canadian and American cities. We found evidence of an impending great urban shift where thousands of species will disappear across the selected cities, being replaced by new species, or not replaced at all. Effects were largely species-specific, with the most negatively impacted taxa being amphibians, canines, and loons. These predicted shifts were consistent across scenarios of greenhouse gas emissions, but our results show that the severity of change will be defined by our action or inaction to mitigate climate change. An impending massive shift in urban wildlife will impact the cultural experiences of human residents, the delivery of ecosystem services, and our relationship with nature.