Potato (Solanum tuberosum L.) is one of the most widely cultivated crops in the world; however, drought is a major constraint to its productivity. Arbuscular mycorrhizal fungi (AMF) have been shown to improve plant resistance under conditions of water stress. However, their effects on potato plants are poorly studied. The purpose of this study was to evaluate the potential of two AMF inocula (two different strains of the AMF species Rhizophagus irregularis with different origin: Southern Spain MI₁ and Tunisia MI₂) on potato tolerance to drought stress through the determination of growth parameters, photosynthetic parameters, and antioxidant systems, under well-watered (WW; field capacity) and drought stress (DS; 50% of field capacity) conditions. Therefore, the experiment consisted of two factors: AMF strain and watering regime. The results showed that under drought stress conditions, AMF inoculation considerably stimulated photosynthetic performance as compared with non-inoculated controls. Moreover, leaf superoxide dismutase (SOD) and catalase (CAT) activities of inoculated plants were higher in WW conditions, but unchanged in DS conditions. Inoculated plants had significantly higher ascorbate peroxidase (APX) and glutathione reductase (GR) activities than non-inoculated plants under DS conditions. Also, expression of some antioxidant enzyme genes were upregulated by inoculation. Lipid peroxidation content of inoculated plants was lower than that of non-inoculated. Furthermore, there was a high positive correlation between mycorrhizal root colonization (RC) and almost all the measured parameters. The results of this study indicated that AMF inoculation could enhance potato plant tolerance to water stress through the induction of antioxidant mechanisms implicated in scavenging oxygen-free radicals.