The proposal of high-quality development strategy raises higher requirements for the comprehensive operation of the eco-economic system. Recent research on high-quality development focuses on the economic subsystem rather than the ecological subsystem or the social subsystem. Moreover, few studies focused on the comprehensive evaluation and spatial pattern of high-quality development of China at the prefecture level. Based on the multi-source data of 306 prefecture level regions in 2018, we first analyzed the connotation of high-quality development and established the indicator system from six dimensions of economic quality, innovation potential, environmental quality, ecological security, people's livelihood, and urban-rural coordination. Then, we calculated the high-quality development index of prefecture level regions, revealed the regional pattern, analyzed the influencing factors, identified the problem areas, and put forward the path to improve the quality of development. The results show that:(1) the high-quality development indices vary significantly across different regions. The development level of the eastern region and the Yangtze River Basin is high, but the development level of the northeastern region and the Yellow River Basin is low. (2) The scores of economic quality, people's livelihood, and innovation potential are low, which is the weak point of high-quality development. (3) The high-quality development has a solid spillover effect, and its comprehensive index is significantly related to the natural environment suitability, city hierarchy, population agglomeration, investment level, transport location, and digital economy. (4) Eight categories and 174 problem regions are identified, which are distributed in 26 provinces, and mainly concentrated in the Yellow River Basin and the Northeast China. Thus, we propose the promotion path of high-quality development from the system construction, national level, and specific regional level, which provides a scientific reference for formulating regional development strategies and policies.