The comprehensive observation system of natural resources has many characteristics, such as multiple objects, indicators, and technical means. In order to ensure the quality of observation data, it is necessary to build a quality management system covering the entire process from collection to publication of data products. Based on the new requirements for a quality management system by the comprehensive observation of natural resources and the analysis of the current situation of quality management systems in the field of observation in China and abroad, this study established a comprehensive observation quality management system framework according to the ISO9001 international standards. The system consists of five parts: target layer, organization layer, regulation layer, control layer, and evaluation layer. Using a modular integration design, this study built a vertical and horizontal multi-level quality control system; established a four-level external inspection process in the vertical direction including the comprehensive center, first level station, second level station, and third level station; and established an observation, proofreading, and review three-level internal inspection process in the horizontal direction. With regard to the quality control technologies, the system focuses on the quality control modules of different observational processes, established four quality control modules: QC0 (sample test quality control module), QC1 (observation data internal quality control module), QC2 (observation data external quality control module), and QC3 (data quality assessment and evaluation module). These modules improve the quality control relevance and effectiveness. By building a comprehensive quality management system and developing scientific quality control methods, this study promotes the long-term and stable development of the comprehensive observation of natural resources.