Spatiotemporal assessment and a comprehensive understanding of cropland sustainability are prerequisites for ensuring food security and promoting sustainable development. However, a remote sensing-based approach framework that is suitable for large-scale and high-precision assessment and can reflect the overall sustainability of cropland has not yet been developed. This study considered a typical lateritic red soil region of Guangdong Province, China, as an example. Cropland sustainability was examined from three aspects: natural capacity, management level, and food productivity. Ten typical indicators, including soil organic matter, pH, irrigation guarantee capability, multiple cropping index, and food productivity, among others, were constructed using remote sensing technology and selected to represent these three aspects. Based on the indicator system, we assessed the spatiotemporal patterns of cropland sustainability from 2010 to 2020. The results showed that the natural capacity, management level, and food productivity of cropland had improved over the 10 years. The cropland sustainability score increased from 67.95 to 69.08 over this period. The sustainability scores for 68.64% of cropland were increased and were largely distributed in the eastern and western region of the study area. The croplands with declining sustainability scores were mostly distributed in the central region. The prefecture-level regions differed in cropland sustainability, with Zhongshan, Zhuhai, and Qingyuan cities exhibiting the highest values, and Zhanjiang the lowest. Exploring the underlying mechanisms of cropland sustainability and proposing improvement measures can guide decision-making, cropland protection, and efficient utilization, especially in similar lateritic red soil regions of the world.