The water footprint (WF), based on irrigation water quality, is important as a decision-making tool for crop selection based on the comparative advantage of water consumption and yield to maximize agricultural water productivity and sustainably improve water use efficiency. This paper presents a generic link between climate variability and water footprint. To support this link, a case study is presented for wheat and maize in different agro-climate zones in Egypt. In this study, the three agro-ecological zones, Nile Delta, Middle Egypt, and Upper Egypt, were selected to represent three different microclimates. The climate data were analyzed to estimate reference evapotranspiration (ETo) and calculate crop water use (CWU) for wheat and maize from 2015 through 2019. Cultivated area and yield data were analyzed during the study period. Water footprint (WF) was calculated for old land (clay soils) and new lands (sandy soils) in three climate regions based on blue and grey water. Green water was excluded due to negligible rainfall depths in Egypt. The results showed that the mean values of WF for maize were 1067, 1395, 1655 m3/ton in old land and 1395, 1634, 2232 m3/ton in new land under the three climate regions, respectively, while it was 923, 982, 1117 m3/ton in old land and 1180, 1258, 1452 m3/ton for wheat in new land for the three regions, respectively. The results show that the crop water use fluctuated over regions due to climate variability where the CWU values were 6211, 7335, 8007 m3/ha for maize and 4348, 4825, 5774 m3/ha for wheat in the three regions, respectively. The results show an 11% and 33% increase in maize and an 18% and 29% increase in wheat CWU in Middle and Upper Egypt regions comparing to what was observed in Nile Delta due to an increase in solar radiation, temperature, and wind speed. The Egypt mean value of wheat water footprint was 1152 m3/ton and mean value of maize water footprint was 1563 m3/ton. The data clearly show the effect of microclimate variability on WF and irrigation requirements between regions. The methodology and results from this study provide a pathway to help the policy makers to mitigate climate change impacts on crop yield and to enhance water resources management in major crop production regions by redistribution of the cropping patterns based on the comparative advantages of each crop within each region. The crop choices relative to the soil water retention characteristics could also contribute to the moderation of microclimate, which affects ETo and ETc and the water footprint. [ABSTRACT FROM AUTHOR]