Abstract: With the accelerated pace of global climate change, the frequent occurrence of extreme weather events such as high temperatures, heavy rains, droughts and low temperatures cause an increased frequency of agro-meteorological disasters, which  poses a huge challenge to the stable supply of grain production. Based on the daily temperature, rainfall meteorological and agricultural production data of 28 cities and municipalities in the Huaihe River Ecological Economic Belt from 2001 to 2020, this paper adopted the linear trend estimation and spatial Durbin model to study the extreme weather variations and the impacts on grain production. The results showed that: (1) The number of extremely high-temperature days (SU35) showed an increasing trend, the number of extremely low-temperature days (FD5) showed a decreasing trend, and the inter-annual tendency rate for SU35 and FD5 were 1.85 days/10a and -2.24 days/10a, respectively. However, the inter-annual trends of rainstorm days (R50) and the longest continuous days without precipitation (CDD) were not significant. The days of SU35 was higher in the central and western regions, while the days of FD5 was higher in the northern regions. The days of RD50 showed a decreasing trend from the east to the central and western regions, and then to the northern regions, while the days of CDD showed the opposite trend. (2) Extreme weather had significantly negative impacts on grain production. 1% increase in the days of FD5, SU35, CDD, and R50, resulted in a decrease of 0.069%, 0.021%, 0.018%, and 0.008% in grain production, respectively. (3) The impact of extreme weather on grain production was regionally heterogeneous. Extreme weather mainly affected grain production in the central and western regions and the northern region, while this impact in the eastern region was not significant. In the future, grain yields stability in the Huaihe River Ecological Economic Belt can be maintained through measures of cultivating new crop varieties that are resistant to drought and flooding, improving the ability to monitor extreme weather changes, strengthening synergistic linkages among region governments, and continuing to maintain high-standard farmland.