Scientifically revealing the spatiotemporal patterns of cultivated land quality (CLQ) is crucial for increasing food production and achieving United Nations Sustainable Development Goal (SDG) 2: Zero Hunger. Although studies on the evaluation of CLQ have been conducted, an effective evaluation system that is suitable for the macro-regional scale has not yet been developed. In this study, we first defined the CLQ from four aspects: soil fertility, natural conditions, construction level, and cultivated land productivity. Then, eight indicators were selected by integrating multi-source remote sensing data to create a new CLQ evaluation system. We assessed the spatiotemporal patterns of CLQ in Guangzhou, China, from 2010 to 2018. In addition, we identified the main factors affecting the improvement of CLQ. The results showed that the CLQ continuously improved in Guangzhou from 2010 to 2018. The area of high-quality cultivated land increased by 13.7%, which was mainly distributed in the traditional agricultural areas in the northern and eastern regions of Guangzhou. The areas of medium- and low-quality cultivated land decreased by 8.1% and 5.6%, respectively, which were scattered throughout the whole study area. The soil fertility and high productivity capacity were the main obstacle factors that affected the improvement of CLQ. Simultaneously, the obstacle degree of stable productivity capacity gradually increased during the study period. Therefore, the targeted improvement measures could be put forward by applying biofertilizers, strengthening crop management and constructing well-facilitated farmland. The new CLQ evaluation system we proposed is particularly practical at the macro-regional scale, and the results provided targeted guidance for decision makers to improve CLQ and promote food security.