Leaf fall disease of rubber tree caused by Neopestalotiopsis cubana has been reported to negatively impact rubber cultivation in southern Thailand. The aim of this study was to test and select effective fungicides to control this disease. Effects of fungicides, namely metalaxyl, prochloraz, hexaconazole, carbendazim, captan, mancozeb, propineb, aironae, copper oxychloride, sulfur, zinc oxide nanoparticles (ZnO NP), and salicylic acid (SA) were tested for inhibition of conidia germination, mycelial growth, and reduction of disease severity index (%). Systemic fungicide 2 x carbendazim suppressed conidia germination (0.67%) and inhibited mycelial growth (100%) more than the other fungicides or control. Furthermore, 2 x carbendazim showed a lesser disease severity index (36.1%) than those other fungicides and control. Enzyme activities of beta-1,3-glucanase, chitinase and peroxidase in carbendazim treated rubber leaves were significantly higher than those observed in control, suggesting that application of carbendazim induced disease resistance in rubber tree leaves. No phytotoxicity (chlorosis, necrosis or leaf blight) was observed in carbendazim treated rubber leaves from level of chlorophyll content. The results reveal that a systemic fungicide, carbendazim, shows antifungal activity against N. cubana, reduces disease development, and induces defense responses in rubber tree leaves.