This study evaluates the effect of climate change on reference evapotranspiration (ET0), which is one of the most important variables in water resources management and irrigation scheduling. For this purpose, daily weather data of 30 Iranian weather stations from 1981 and 2010 were used. The HadCM3 statistical model was applied to report the output subscale of LARS-WG and to predict the weather information by A1B, A2, and B1 scenarios in three periods: 2011–2045, 2046–2079, and 2080–2113. The ET0 values were estimated by the Ref-ET software. The results indicated that the ET0 will rise from 2011 to 2113 approximately in all stations under three scenarios. The ET0 changes percentages in the A1B scenario during three periods from 2011 to 2113 were found to be 0.98%, 5.18%, and 12.17% compared to base period, respectively, while for the B1 scenario, they were calculated as 0.67%, 4.07%, and 6.61% and for the A2 scenario, they were observed as 0.59%, 5.35%, and 9.38%, respectively. Thus, the highest increase of the ET0 will happen from 2080 to 2113 under the A1B scenario; however, the lowest will occur between 2046 and 2079 under the B1 scenario. Furthermore, the assessment of uncertainty in the ET0 calculated by the different scenarios showed that the ET0 predicted under the A2 scenario was more reliable than the others. The spatial distribution of the ET0 showed that the highest ET0 amount in all scenarios belonged to the southeast and the west of the studied area. The most noticeable point of the results was that the ET0 differs from one scenario to another and from a period to another.