Sesame is one of the important oil seed crops grown for the high-quality oil. Its growth, development, and yield are significantly affected by the changing climate conditions. Evaluating the sesame climatic suitability is crucial to optimize sesame cultivation patterns and planting distribution, and to aid strategic decision making for future agricultural adaptation. Based on agricultural climatic suitability theory and the fuzzy mathematics method, in this study, we established the temperature, precipitation, sunshine, and comprehensive suitability model. Then, we assessed the spatial distribution and chronological changes in climatic suitability under two periods, 1978–1998 (earlier 21 years) and 1999–2019 (latter 21 years). The results showed that compared with the meteorological data in the earlier 21 years, the mean temperature during the sesame-growing season in the latter 21 years increased from 24.48 °C to 25.05 °C, and the cumulative precipitation increased from 744.38 mm to 754.81 mm; however, the sunshine hours decreased from 6.05 h to 5.55 h. Temperature, precipitation, sunshine, and comprehensive suitability during the sesame-growing season in the main sesame-producing areas of China all had a downward trend. The distribution of temperature and comprehensive suitability in the north is higher than that in the south, while the precipitation and sunshine suitability had an uneven distribution. The area of high-temperature suitability and high-precipitation suitability increased from 43.45 × 106 ha to 46.34 × 106 ha and from 3.20 × 106 ha to 7.97 × 106 ha, respectively, whereas the area of high-sunshine suitability decreased from 4.04 × 106 ha to 2.09 × 106 ha. The climate change was more beneficial to sesame cultivation in northeast Anhui where the area of high climatic suitability clearly expanded, and in eastern Jiangxi where the area of the general climatic suitability increased. In contrast, it is worth noting that the area of high climatic suitability in northern Henan decreased and the area of low climatic suitability in Hubei increased. Our results have important implications for improving agricultural production to cope with ongoing climate change.