The extensive postglacial mammal losses in the West Indies provide an opportunity to evaluate extinction dynamics, but limited data have hindered our ability to test hypotheses. Here, we analyze the tempo and dynamics of extinction using a novel data set of faunal last-appearance dates and human first-appearance dates, demonstrating widespread overlap between humans and now-extinct native mammals. Humans arrived in four waves (Lithic, Archaic, Ceramic, and European), each associated with increased environmental impact. Large-bodied mammals and several bats were extinct by the Archaic, following protracted extinction dynamics perhaps reflecting habitat loss. Most small-bodied rodents and lipotyphlan insectivores survived the Ceramic, but extensive landscape transformation and the introduction of invasive mammals following European colonization caused further extinctions, leaving a threatened remnant fauna. Both large- and small-bodied nonvolant mammals disappeared, reflecting complex relationships between body size, ecology, and anthropogenic change. Extinct bats were generally larger species, paralleling declines from natural catastrophes.