Nanomaterials offer considerable benefits in improving plant growth and nutritional status owing to their inherent stability, and efficiency in essential nutrient absorption and delivery. Cerium oxide nanoparticles (CeO2 NPs) at optimum concentration could significantly influence plant morpho-physiology and nutritional status. However, it remains unclear how elevated CO2 and CeO2 NPs interactively affect plant growth and quality. Accordingly, the ultimate goal was to reveal whether CeO2 NPs could alter the impact of elevated CO2 on the nutrient composition of spinach. For this purpose, spinach plant morpho-physiological, biochemical traits, and nutritional contents were evaluated. Spinach was exposed to different foliar concentrations of CeO2 NPs (0, 25, 50, 100 mg/L) in open-top chambers (400 and 600 CO2 μmol/mol). Results showed that elevated CO2 enhanced spinach growth by increasing photosynthetic pigments, as evidenced by a higher photosynthetic rate (Pn). However, the maximum growth and photosynthetic pigments were observed at the highest concentration of CeO2 NPs (100 mg/L) under elevated CO2. Elevated CO2 resulted in a decreased stomatal conductance (gs) and transpiration rate (Tr), whereas CeO2 NPs enhanced these parameters. No significant changes were observed in any of the measured biochemical parameters due to increased levels of CO2. However, an increase in antioxidant enzymes, particularly in catalase (CAT; 14.37%) and ascorbate peroxidase (APX; 10.66%) activities, was observed in high CeO2 NPs (100 mg/L) treatment under elevated CO2 levels. Regarding plant nutrient content, elevated CO2 significantly decreases spinach roots and leaves macro and micronutrients as compared to ambient CO2 levels. CeO2 NPs, in a dose-dependent manner, with the highest increase observed in 100 mg/L CeO2 NPs treatment and increased roots and shoots magnesium (211.62–215.49%), iron (256.68–322.77%), zinc (225.89–181.49%), copper (21.99–138.09%), potassium (121.46–138.89%), calcium (118.22–91.32%), manganese (133.15–195.02%) under elevated CO2. Overall, CeO2 NPs improved spinach growth and biomass and reverted the adverse effects of elevated CO2 on its nutritional quality. These findings indicated that CeO2 NPs could be used as an effective approach to increase vegetable growth and nutritional values to ensure food security under future climatic conditions.