Microplastic debris is a globally ubiquitous pollutant with diverse consequences for fishes, ranging from severe negative impacts to neutral, or even, positive effects. In the present study, we conducted a systematic review and meta‐analysis of experimental and observational studies to test for the impacts of microplastic exposure on freshwater, estuarine and marine fishes across diverse taxonomies, geographies, and ecosystem contexts. We report evidence for the detrimental, albeit variable, impacts of microplastics, including reduced consumption, altered feeding behavior, obstructed digestion and assimilation, decreased growth, and compromised immunity. By contrast, microplastics appeared to invoke neutral responses in several other ecological and physiological processes, such as body condition, fecundity, hatching success and survival. The results from this study also point to the mismatch between the types, shapes, and sizes of microplastics investigated in experimental settings versus those found in fish in the wild, as well as a striking difference between the 728 fish species investigated for microplastic contamination in the wild versus the only 22 fish species evaluated for the effects of microplastics in the laboratory. The present study reiterates the necessity for more consistent methodological approaches to analyzing and reporting the effects of microplastic exposure, including greater taxonomic breadth and the use of environmentally relevant polymers in future studies. Furthermore, model simulations that explore individual‐ and population‐level implications of realistic exposure scenarios are needed. Overall, the current weight of evidence supports continued management and policy actions to reduce the microplastic production, use, and release into the world's waters.