Integrated environmental management has been world widely treated as a fundamental means to support sustainable development. However, linking theoretical models to local practices in an effective framework remains to be a key challenge of such management. This study aimed to address progresses on technical development and practices of the integrated environmental regulation in China. We presented a new conceptual framework of the "Three Lines One Permit" (TLOP) Policy by combining a red line for ecological conservation (RLEC), a bottom line for environmental quality (BLEQ), an upper-limit line for resource use (ULRU), and a list of environmental permits for human activities (LEP). We also described the main achievements and effectiveness by a case study in the Yangtze River Economic Belt (YREB). Nearly 50% of the total territory of the YREB was designated as ecological space, including 29.4% of RLEC and 19.4% of ordinary ecological space. Over 9,800 water regulatory zones and 10,600 atmospheric regulatory zones were partitioned with environmental objectives and measures. There were over 15,000 integrated regulatory units with a multi-component list of environmental permits, in which 6,400 critical regulatory units contained all constructed urban areas, more than 280 million people, and 1,200 industrial parks. These integrated and spatially varied environmental regulatory units of TLOP will help to establish a preventive mechanism for ecological conservation, resource explorations, and emissions control. Suggestions were proposed to promote a more flexible and efficient policy toward the ecological civilization and sustainable development strategies.