Abstract: Clarifying the vulnerability status of cropland use system is an effective way to respond to systemic crises. Taking the Huaihai Economic Zone as an example, this article constructed a set of assessment system of cropland use vulnerability under urbanization disturbance from three aspects: exposure, sensitivity, and adaptability. This study revealed the spatio-temporal evolution of cropland use vulnerability at the county level from 2000 to 2018. The regional types were divided according to the characteristics of cropland use vulnerability, and targeted regulation strategies were proposed. The findings showed that: (1) The overall vulnerability of cropland use had shown a gradual growth trend, mainly due to the insufficient carrying capacity of the internal adaptability of cropland use for the cropland use exposure. (2) The spatial distribution of cropland use exposure had shifted from being dominated by low-value counties to being dominated by high-value counties; the spatial distribution of sensitivity and adaptability of cropland use had been dominated by low-value counties, while both had increased in most counties; Collectively, the spatial distribution of cropland use vulnerability showed the dominance of low-value counties and the spread of high-value counties. (3) Based on the structural characteristics of cropland use vulnerability, the Huaihai Economic Zone was classified into seven types of regions, and corresponding targeted strategies were proposed to alleviate the contradiction between urbanization and cropland protection and to promote the healthy and sustainable development of cropland use system.