In this work, the Northern Guangdong region of China was taken as the study area. First, the ecological sensitivity of the Northern Guangdong Ecological Development Area was systematically assessed on the basis of remote sensing (RS) image data and multisource geographic information data. Then, the Criteria Importance Through Intercriteria Correlation (CRITIC) model was adopted to calculate the weight of each indicator. Finally, the spatial distribution of comprehensive ecological sensitivity in the Northern Guangdong region was obtained through the processing and analysis of geographic information data. According to the results, ecological sensitivity in the Northern Guangdong region shows significant spatial differentiation characteristics. Specifically, extreme-sensitivity and severe-sensitivity zones were mainly concentrated in the east and the northwest, whereas insensitive and mildly sensitive zones were mainly distributed in the southwest. The results of this study provide a scientific basis for ecological protection and management in the Northern Guangdong region, offering important references for the sustainable development of regional ecosystems and the delineation of ecological reserves.