Southern corn rust caused by Puccinia dothidea is becoming one of the main diseases of maize planting in China, which seriously threatens the yield of maize in China. Currently, there is no registered pesticide to control southern corn rust in China. Therefore, it is urgent to screen out efficient pesticides to control southern corn rust and reduce the harm of multistem rust to maize yield in China. In the present study, the indoor virulence determination of spore-germination method and 2 years of field efficacy tests were used to screen the fungicides with good prevention and control efficacy on maize southern rust. The results of the indoor toxicity test in 2023 showed that the EC50 of P. dothidea to benzoflumizole was 0.0085 mg/L, and the sensitivity to thifluzamide was relatively poor, with an EC50 of 1.2585 mg/L. The mixture of pyraclostrobin and benzoflumizole at a ratio of 4:1 had the optimal synergistic effect, with an EC50 of 0.0181 mg/L and a cotoxicity coefficient of 128.36. The results of the field efficacy test revealed that 60 g/ha benzovinfluconazole had a good field control effect, and the control effect was 83.09%–85.95%. The combination of 30 g/ha benzodifluconazole and 93.75 g/ha pyraclostrobin had the optimal control effect, and the control effect was 86.92%–88.58% and safe for corn. The results indicated that the application of benzovindiflupyr and its mixture with pyraclostrobin had a good effect on the prevention and control of southern corn rust, which could provide a theoretical basis for the prevention and control of southern corn rust in production and scientific medication.