Most ectothermic organisms mature at smaller body sizes when reared in warmer conditions. This phenotypically plastic response, known as the "temperature-size rule" (TSR), is one of the most taxonomically widespread patterns in biology. However, the TSR remains a longstanding life-history puzzle for which no dominant driver has been found. We propose that oxygen supply plays a central role in explaining the magnitude of ectothermic temperature-size responses. Given the much lower oxygen availability and greater effort required to increase uptake in water vs. air, we predict that the TSR in aquatic organisms, especially larger species with lower surface area-body mass ratios, will be stronger than in terrestrial organisms. We performed a meta-analysis of 1,890 body mass responses to temperature in controlled experiments on 169 terrestrial, freshwater, and marine species. This reveals that the strength of the temperature-size response is greater in aquatic than terrestrial species. In animal species of ∼100 mg dry mass, the temperature-size response of aquatic organisms is 10 times greater than in terrestrial organisms (-5.0% °C(-1) vs. -0.5% °C(-1)). Moreover, although the size response of small (<0.1 mg dry mass) aquatic and terrestrial species is similar, increases in species size cause the response to become increasingly negative in aquatic species, as predicted, but on average less negative in terrestrial species. These results support oxygen as a major driver of temperature-size responses in aquatic organisms. Further, the environment-dependent differences parallel latitudinal body size clines, and will influence predicted impacts of climate warming on food production, community structure, and food-web dynamics.