The study used a modelling approach to assess the potential impacts of likely climate change and increase in CO2 concentration on the wheat growth and water balance in Murray'Darling Basin in Australia. Impacts of individual changes in temperature, rainfall or CO2 concentration as, well as the 2050 and 2070 climate change scenarios, were analysed. Along an E'W transect, wheat yield at western sites (warmer and drier) was simulated to be more sensitive to temperature increase than that at eastern sites; along the S'N transect, wheat yield at northern warmer sites was simulated to be more sensitive to temperature increase, within 1'3°C temperature increase. Along the E'W and S'N transects, wheat at drier sites would benefit more from elevated [CO2] than at wetter sites, but more sensitive to the decline in rainfall. The increase in temperature only did not have much impact on water balance. Elevated [CO2] increased the drainage in all the sites, whilst rainfall reduction decreased evapotranspiration, runoff and drainage, especially at drier sites. In 2050, wheat yield would increase by 1'10% under all climate change scenarios along the S' N transect, except for the northernmost site (Dalby). Along the E'W transect, the most obvious increase of wheat yields under all climate change scenarios occurred in cooler and wetter eastern sites (Yass and Young), with an average increase rate of 7%. The biggest loss occurred at the driest sites (Griffith and Swan Hill) under A1FI and B2 scenarios, ranging from '5% to '16%. In 2070, there would be an increased risk of yield loss in general, except for the cool and wet sites. Water use efficiency was simulated to increase at most of the study sites under all the climate change scenarios, except for the driest site. Yield variability would increase at drier sites (Ardlethan, Griffith and Swan Hill). Soil types would also impact on the response of wheat yield and water balance to future climate change.