Non-native species and climate change pose serious threats to global biodiversity. However, the roles of climate, dispersal, and competition are difficult to disentangle in heterogeneous landscapes. We combine empirical data and theory to examine how these forces influence the spread of non-native species in Lake Baikal. We analyze the potential for Daphnia longispina to establish in Lake Baikal, potentially threatening an endemic, cryophillic copepod Epischurella baikalensis. We collected field samples to establish current community composition and compared them to model predictions informed by flow rates, present-day temperatures, and temperature projections. Our data and model agree that expansion is currently limited by dispersal. However, projected increases in temperature reverse this effect, allowing D. longispina to establish in Lake Baikal’s main basin. A strong negative impact emerges from the interaction between climate change and dispersal, outweighing their independent effects. Climate, dispersal, and competition have complex, interactive effects on expansion with important implications for global biodiversity.