Changes in cultivated land use significantly impact food production capacity, which in turn affects food security. Therefore, accurately understanding the spatial and temporal variations in cultivated land use is critical for strategic decision-making regarding national food security. Since the second national soil survey was conducted in around 1980, China has implemented major efforts, such as a nationwide soil testing and fertilization project in around 2005 and the establishment of the National Standards for Cultivated Land Quality Grading in 2016. However, limited research has focused on how cultivated land use has changed during these periods and the mechanisms driving these changes. This study, using Enshi Prefecture in the mountainous region of southwestern Hubei Province as a case study, examines the spatiotemporal changes in cultivated land use during 1980–2018. Land use data from 1980, 2005, and 2018 were combined with statistical yearbook data from Enshi Prefecture, and remote sensing and GIS technology were applied. Indicators such as the dynamic degree of cultivated land use, the relative rate of change in cultivated land use, and a Geoscience Information Atlas model were used to explore these changes. Additionally, principal component analysis was employed to examine the mechanisms influencing these changes. The results show that (1) the area of cultivated land in Enshi Prefecture increased slightly from 1980 to 2005, while from 2005 to 2018, it significantly decreased; compared with the earlier period, the transformation of land use types during 2005–2018 was more intense; (2) the increase in cultivated land area from 1980 to 2005 was mainly due to deforestation, the creation of farmland from lakes, and the reclamation of wasteland, while the decrease in land area was primarily attributed to the conversion of farmland back to forests and grassland. From 2005 to 2018, the main drivers for the increase in cultivated land were deforestation and the reclamation of wasteland, while the return of farmland to forests remained the primary reason for the decrease in land area; (3) from 1980 to 2005, the dynamic degree of cultivated land use in each county and city of Enshi Prefecture was generally low. However, between 2005 and 2018, the dynamic degree increased in most counties and cities except Enshi City and Xianfeng County; (4) there were significant variations in the relative rate of change in cultivated land utilization across counties and cities from 1980 to 2005. However, from 2005 to 2018, the relative rate of change decreased in all counties and cities compared to the previous period; (5) since 1980, nearly 50% of the cultivated land in Enshi Prefecture has undergone land classification conversion, with frequent shifts between different land classes; and (6) economic development, population growth, capital investment, food production, and production efficiency are the dominant socioeconomic factors driving changes in cultivated land use in Enshi Prefecture. The results of this study can provide a scientific basis for the protection and optimization of cultivated land resources in the mountainous regions of southwestern Hubei Province.