Recently, there has been considerable attention towards the production of environmentally friendly nanoparticles (NPs). In this investigation, the successful synthesis of cerium oxide nanoparticles (CeO2 NPs) was achieved by employing an eco-friendly technique that utilized an extract from the leaves of local plant quinoa (Chenopodium quinoa L.). The synthesized CeO2 NPs were subjected to characterization using state-of-the-art methods. The prepared CeO2 NPs contained a round shape with clusters and have a size of 7-10 nm. To assess how effective CeO2 NPs derived from C. quinoa were against Ustilago tritici, a fungal disease that negatively affects wheat crop globally, a study was performed on two varieties of wheat crop comprised of Arooj (V1) and Akber (V2), cultivated under field conditions. CeO2 NPs were applied foliarly twice to the wheat crop at four different concentrations: T0 (0 mg/L), T1 (50 mg/L), T2 (75 mg/L), and T3 (100 mg/L). The results revealed that the control group (T0) exhibited the highest disease severity index (DSI) with a value of 75% compared to the other concentrations of CeO2 NPs on both varieties. At a concentration of 100 mg/L of CeO2 NPs, the DSI dropped to a minimum of 35% and 37% on both V1 and V2 respectively. These findings indicated that an increase in the concentration of CeO2 NPs has a beneficial impact on disease severity. Similar patterns have also been observed with disease incidence (DI), with the greatest efficacy observed at a concentration of 100 mg/L of CeO2 NPs. Our investigation has shown that CeO2 NPs exhibitd significant antifungal potential against U. tritici which may be a promising strategy to mitigate fungal disease and crop losses globally.