Prey naiveté-the failure of prey to recognize novel predators as threats-is thought to exacerbate the impact that exotic predators exert on prey populations. Prey naiveté varies under the influence of eco-evolutionary mediating factors, such as biogeographic isolation and prey adaptation, although an overall quantification of their influence is lacking. We conducted a global meta-analysis to test the effects of several hypothesized mediating factors on the expression of prey naiveté. Prey were overall naive towards exotic predators in marine and freshwater systems but not in terrestrial systems. Prey naiveté was most pronounced towards exotic predators that did not have native congeneric relatives in the recipient community. Time since introduction was relevant, as prey naiveté declined with the number of generations since introduction; on average, around 200 generations may be required to erode naiveté sufficiently for prey to display antipredator behaviour towards exotic predators. Given that exotic predators are a major cause of extinction, the global predictors and trends of prey naiveté presented here can inform efforts to meet conservation targets.