Our study first reveals that Mo mediates oxidative tolerance through ABA signaling. Moreover, NO acts downstream of ABA signaling in Mo-induced oxidative tolerance in wheat under drought stress. Nitric oxide (NO) is related to the improvement of molybdenum (Mo)-induced oxidative tolerance. While the function of Mo in abscisic acid (ABA) synthesis and in mediating oxidative tolerance by the interaction of ABA and NO remain to be studied. The -Mo and +Mo treatment-cultivated wheat was separated and subsequently was pretreated with AO inhibitor, ABA synthesis inhibitor, exogenous ABA, NO scavenger, NO donor or their combinations under polyethylene glycol 6000 (PEG)-stimulated drought stress (PSD). The AO activity and ABA content were increased by Mo in wheat under PSD, however, AO inhibitor decreased AO activity, correspondingly reduced ABA accumulation, suggesting that AO involves in the regulation of Mo-induced ABA synthesis. Mo enhanced activities and expressions of antioxidant enzyme, while these effects of Mo were reversed by AO inhibitor and ABA synthesis inhibitor due to the decrease of ABA content, but regained by exogenous ABA, indicating that Mo induces oxidative tolerance through ABA. Moreover, NO scavenger inhibited activities of antioxidant enzyme caused by Mo and exogenous ABA, but the inhibitions were eliminated by NO donor, indicating that NO is involved in ABA pathway in the regulation of Mo-induced oxidative tolerance in wheat under PSD. Finally, we proposed a scheme for the mechanism of Mo-induced oxidative tolerance.