Understanding the mechanisms by which nonnative species successfully invade new regions and the consequences for native fauna is a pressing ecological issue, and one for which niche theory can play an important role. In this paper, we quantify a comprehensive suite of morphological, behavioral, physiological, trophic, and life-history traits for the entire fish species pool in the Colorado River Basin to explore a number of hypotheses regarding linkages between human-induced environmental change, the creation and modification of ecological niche opportunities, and subsequent invasion and extirpation of species over the past 150 years. Specifically, we use the fish life-history model of K. O. Winemiller and K. A. Rose to quantitatively evaluate how the rates of nonnative species spread and native species range contraction reflect the interplay between overlapping life-history strategies and an anthropogenically altered adaptive landscape. Our results reveal a number of intriguing findings. First, nonnative species are located throughout the adaptive surface defined by the life-history attributes, and they surround the ecological niche volume represented by the native fish species pool. Second, native species that show the greatest distributional declines are separated into those exhibiting strong life-history overlap with nonnative species (evidence for biotic interactions) and those having a periodic strategy that is not well adapted to present-day modified environmental conditions. Third, rapidly spreading nonnative fishes generally occupy “vacant” niche positions in life-history space, which is associated either with “niche opportunities” provided by human-created environmental conditions (consistent with the environmental-resistance hypothesis of invasion) or with minimal overlap with native life-history strategies (consistent with the biotic-resistance hypothesis). This study is the first to identify specific life-history strategies that are associated with extensive range reduction of native species and expansion of nonnative species, and it highlights the utility of using niche and life-history perspectives to evaluate different mechanisms that contribute to the patterns of fish invasions and extirpations in the American Southwest.