Abstract: The ecological security of cultivated land is the cornerstone for ensuring food security and ecological civilization construction. Through scientific evaluation, it is conducive to promoting the realization of the coordinated goals of “preserving quantity, improving quality and protecting ecology” of cultivated land resources. This study constructed an ecological security index system for cultivated land using the pressure-state-response (PSR) model. By combining the combination weighting method and the comprehensive index method, the spatio-temporal changes in the ecological security of cultivated land in Anhui Province from 2010 to 2020 were evaluated. Meanwhile, the obstacle degree model was used to divide the protection pattern zones of cultivated land ecological security and explore the obstructive factors affecting the cultivated land ecological security in various cities of Anhui Province. The results show that: 1) From 2010 to 2020, the score of the pressure subsystem of cultivated land ecological security in Anhui Province first decreased and then increased, the score of the state subsystem showed fluctuating improvement, while the score of the response subsystem showed a downward trend. The areas with low scores in each subsystem expanded to varying degrees. 2) The ecological security of cultivated land was stable on the time scale, with the score fluctuating slightly around 0.48. Overall, it was at the critical security level. In terms of spatial scale, the heterogeneity was obvious, showing a relatively significant “layered” pattern, that is, the ecological security status of cultivated land in the area centered on Hefei City is significantly lower than that in other areas. 3) The main obstacle factors in the pressure subsystem were cultivated land area per capita, population density and pesticide load per unit of cultivated land. The main obstacle factors in the state subsystem were multiple cropping index, land reclamation rate, and share of primary industry in GDP. The main obstacle factors in the response subsystem were proportion of agricultural fisical expenditure, forest coverage and disposable income of rural residents. In conclusion, Anhui Province should focus on adjusting the agricultural industrial structure, leveraging regional advantages, reducing the use of pesticide, and increasing investment in agricultural development funds, to promote green agricultural development, optimize the ecological security service function of cultivated land, and achieve sustainable development of cultivated land resources.