Drought is a major environmental event affecting crop productivity and nutritional quality, and potentially, human nutrition. This study evaluated drought effects on performance and nutrient acquisition and distribution in sorghum; and whether ZnO nanoparticles (ZnO-NPs) might alleviate such effects. Soil was amended with ZnO-NPs at 1, 3, and 5 mg Zn/kg, and drought was imposed 4 weeks after seed germination by maintaining the soil at 40% of field moisture capacity. Flag leaf and grain head emergence were delayed 6-17 days by drought, but the delays were reduced to 4-5 days by ZnO-NPs. Drought significantly (p < 0.05) reduced (76%) grain yield; however, ZnO-NP amendment under drought improved grain (22-183%) yield. Drought inhibited grain nitrogen (N) translocation (57%) and total (root, shoot and grain) N acquisition (22%). However, ZnO-NPs (5 mg/kg) improved (84%) grain N translocation relative to the drought control and restored total N levels to the non-drought condition. Shoot uptake of phosphorus (P) was promoted (39%) by drought, while grain P translocation was inhibited (63%); however, ZnO-NPs lowered total P acquisition under drought by 11-23%. Drought impeded shoot uptake (45%), grain translocation (71%) and total acquisition (41%) of potassium (K). ZnO-NP amendment (5 mg/kg) to drought-affected plants improved total K acquisition (16-30%) and grain K (123%), relative to the drought control. Drought lowered (32%) average grain Zn concentration; however, ZnO-NP amendments improved (94%) grain Zn under drought. This study represents the first evidence of mitigation of drought stress in full-term plants solely by exposure to ZnO-NPs in soil. The ability of ZnO-NPs to accelerate plant development, promote yield, fortify edible grains with critically essential nutrients such as Zn, and improve N acquisition under drought stress has strong implications for increasing cropping systems resilience, sustaining human/animal food/feed and nutrition security, and reducing nutrient losses and environmental pollution associated with N-fertilizers.