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Changes in environmental conditions often reverse outcomes of competitive interactions among species. Such context dependency implies that the speed, persistence, and ubiquity of anthropogenic habitat alterations may suddenly put even previously well-adapted native species at a competitive disadvantage with non-native species. That is, anthropogenic disturbance may so drastically alter environments that a native species finds itself in an environment that in key ways is just as novel as it is to a non-indigenous species. Extreme disturbances may thereby erase a native species’ prior advantage of local environmental adaptation accrued during its long-term incumbency over evolutionary time. I document examples from two areas of dramatic human alteration of selection regimes – eutrophication and the selective removal of top predators – that support this mechanism. Additionally, I highlight ways in which this mechanism is experimentally testable. Alteration of selection regimes may prove to be a powerful explanation for the enhanced success and impact of biological invasions in our globally disturbed biosphere.