Regional detection of a greenhouse warming signal relies on extensive, long-term measurements of temperature. The potentially confounding impact of land-cover and land-use change on trends in temperature records has mostly focused on the influence of urban heat islands. Here we use a regional climate model to show that a regional irrigation cooling effect (ICE) exists, opposite in sign to urban heat island effects. The magnitude of the ICE has strong seasonal variability, causing large dry-season decreases in monthly mean and maximum temperatures, but little change in rainy-season temperatures. Our model produced a negligible effect on monthly minimum temperature. In California, the modeled regional ICE is of similar magnitude, but opposite sign, to predictions for future regional warming from greenhouse gases. Given our results for California and the global importance of irrigated agriculture, past expansion of irrigated land has likely affected observations of surface temperature, potentially masking the full warming signal caused by greenhouse gas increases.