Corynespora leaf spot is sesame common disease, seriously affecting the yield and quality of the sesame. To determine the optimal period of prevention and control of Corynespora leaf spot and formulate effective pesticide control measures, the occurrence of Corynespora leaf spot in Pingyu County was monitored from 2017 to 2019. The indoor toxicity and field control efficiency of 16 fungicides were determined. The results showed that the initial occurrence stage of Corynespora leaf spot was the squaring stage-early flowering stage, and the turning stage of disease development was the early flowering stage-full flowering stage （20-31, July, in Huanghuai region, the incidence was less than 3% or the disease index was less than 1）. Among the 16 fungicides, hexaconazole, prochloraz, flusilazole, tebuconazole, difenoconazole, procymidone, thiofuramide and fludioxonil were the stronger toxicity to Corynespora leaf spot, EC50 is 1.5734×10-4, 0.1248, 0.7128, 1.3922, 2.0014, 2.7323, 5.4327 and 6.1285 mg/L. Thiofuramide, hexaconazole, azoxystrobin, tebuconazole and difenoconazole had well field efficacy both on disease control and yield improvement. The control efficacies were 67.19%, 65.86%, 61.17%, 60.87% and 61.83%, the increase rates were 38.96%, 36.86%, 39.72%, 34.96% and 38.56%, respectively. The control efficacy and yield increase efficacy of difenoconazole, hexaconazole, azoxystrobin and tebuconazole were the best when applied twice. According to the results, the optimal control period of Corynespora leaf spot in sesame was from early flowering stage to full flowering stage as 20-31 July in Huanghuai region, or before the disease incidence reached 3% or disease index reached 1. Thus it is supposed to select thiofuramide, hexaconazole, azoxystrobin, tebuconazole and difenoconazole as fungicides. The same fungicide should not be applied for more than twice with an interval of 10 days. In order to reduce fungicide residues and prevent pathogens from producing resistance （tolerance）, different fungicides could be used alternately.