By constructing an evaluation system for the high-quality development of innovation and entrepreneurship, an evaluation index system was established in this study from five aspects: the background, process, input, output, and transformation of innovation and entrepreneurship, and analytic hierarchy process (AHP) and entropy method (EM) were adopted to perform combination weighting. Then, the core of each subsystem and the comprehensive score were calculated based on the TOPSIS method, the high-quality development level of urban innovation and entrepreneurship in 19 vice-ministerial cities like Beijing, Shanghai, Tianjin, Chongqing, Guangzhou, Shenzhen, and Chengdu in China was measured, and the innovation and entrepreneurship development level and structural characteristics were analyzed from five aspects. The results show that Shenzhen, Shanghai, Beijing, Nanjing, and Guangzhou take the lead in the high-quality development of innovation and entrepreneurship, while Xi’an, Chengdu, Hangzhou, Wuhan, Qingdao, Jinan, and Ningbo are in the medium level. Chongqing, Shenyang, Dalian, Harbin, Xiamen, and Changchun perform poorly in the development of innovation and entrepreneurship with problems of interregional large gradient difference in capacity and unbalanced development, which provides an important reference for understanding the current situation, advantages, and disadvantages of innovation and entrepreneurship education development in various economic zones.