Here we identified and evaluated the strengths and spatio-temporal heterogeneities in 12 main socio-economic driving factors of water footprints and inter-provincial virtual water flows related to three staple crops (rice, wheat, and maize) within mainland China for 2000–2017, in consideration of the infrastructure related to irrigation, agricultural electricity and road for the first time. The irrigation, agricultural electricity, and road infrastructures in China expanded by 33.8, 4.5, and 2.4 folds, respectively, throughout the course of this study. The results show that irrigation infrastructure in water-scarce regions was the most critical driver for the effective reduction of the water footprint per unit mass of crops, particularly the blue water footprints (i.e. increasing water efficiency). As the irrigation infrastructure per unit area doubled for 2000–2008, blue water use efficiency and total blue water consumption decreased by 58% and 71%, respectively. However, the development of irrigation infrastructure has led to a larger total water footprint in crop production. Agricultural electricity and road infrastructures had increasing effects on provincial virtual water export, with varied corresponding driving strengths across spaces. The visible effects of agricultural infrastructure on regional water productivity, water consumption, and virtual water patterns should not be neglected. This analysis suggests that investments in agricultural infrastructure should consider the spatio-temporal heterogeneity of these infrastructures on local water productivity and water consumption in addition to the economic benefits.