Due to the increasingly complex global climatic environment and the rapid development of China’s urban construction, China’s historical and cultural cities are experiencing an external impact as well as internal fragility. Representing the capacity of the urban system to address impact and pressure, resilience can effectively guarantee the sustainable development of historical and cultural cities. A scientific and reasonable resilience assessment system can guide the resilience construction of historical and cultural cities in an effort to effectively counter the impact and pressure they face. Therefore, it is necessary to research the resilience of historical and cultural cities. On the basis of the complex adaptive system (CAS), and by applying multiple assessment indicators, this paper established a resilience assessment system for China’s historical and cultural cities, comprising 38 indicators in six dimensions, to analyze the characteristics and the influencing mechanisms of the resilience of the historical and cultural cities and to reveal the inherent logic underlying their complex presentation. Using six historical and cultural cities in east China as an example, the study applied the assessment system to assess and analyze the different resilience levels of the cities. The comprehensive resilience of Changzhou City obtained the highest score at 0.64, indicating a higher degree of resilience; the scores of Yantai City, Huzhou City, and Nantong City were 0.59, 0.54, and 0.50, respectively, representing moderate degrees of resilience; the scores of Zhongshan City and Quzhou City were 0.44 and 0.40, respectively, exhibiting a lower degree of resilience. Moreover, the factors that result in an unbalanced development of urban resilience were explored from the perspectives of economy, system, and culture. The paper contains some significance in guiding the development of the resilience of historical and cultural cities.