Flash droughts adversely affect agriculture and ecosystems due to their rapid depletion of soil moisture (SM). However, few studies assessed the impacts of flash droughts on crops, especially in the agricultural regions of southern China. In this study, we investigated flash droughts using crop root zone SM in the main agricultural region of southern China. Additionally, solar-induced chlorophyll fluorescence (SIF) served as a vegetation index to explore the crop response to flash droughts. The results reveal that the SIF exhibited an upward trend from 2001 to 2020 in the study area, indicating the enhanced photosynthetic capacity of crops and subsequent yield improvement. Hotspots of flash drought frequency occurred in the eastern areas of both the upper and lower Yangtze River regions, specifically in areas where the most rapid types of flash droughts were particularly prevalent. The average duration of flash droughts in the southern agricultural region was 6–12 pentads, a sufficiently long duration to significantly hinder crop photosynthesis, resulting in negative SIF standardized anomalies. The area affected by flash droughts in the southern agricultural region presented a downward trend during 2001–2020, with flash droughts of the longest duration in the recent decade, specifically in 2019, 2010, and 2013. The response frequency and time of SIF to flash droughts were >80% and <2 pentads, respectively, indicating that crops in the study area have a high sensitivity to flash droughts. In the northern part of the middle Yangtze River region and the southwestern and southeastern parts of the South China region, the mean values of the standardized anomalies of the SIF were lower than −0.5 during flash droughts, suggesting that crops in these areas were severely affected by flash droughts. During the late summer of 2019, the study area experienced a precipitation shortage coupled with high evapotranspiration capacity. This unfavorable combination of meteorological conditions can quickly lead to a substantial depletion of SM, ultimately triggering flash droughts that can be devastating for crops. Our findings can enhance the understanding of the impacts of flash droughts on crops in agricultural regions, as well as provide early warning signals of flash droughts for farmers to make appropriate mitigation strategies.