Objective This study was aimed at understanding Yangzhou residents’ awareness regarding core knowledge of chronic disease prevention and control, to provide a scientific basis for formulating a publicity plan to support chronic disease prevention and control in Yangzhou. Methods In April 2021, 5 419 questionnaires regarding core knowledge of chronic disease prevention and control were collected through multi-stage stratified random sampling. Residents’ core knowledge of chronic disease prevention and control, and the factors influencing this knowledge, were analyzed. Results The awareness rate regarding core knowledge of chronic disease prevention and control among Yangzhou residents was 69.18%. Multivariate logistic regression analysis indicated that female sex (OR=1.163), older age (OR=1.015), high education level (senior high school OR=1.285, college degree or above OR=2.211), professional and technical employment (OR=1.750), and attending health lectures related to chronic diseases in the prior 3 years (OR=2.420) were associated with higher awareness rates (all P<0.001). Conclusions The awareness rate of core information of chronic diseases was low in Yangzhou City, gender, age, education level, professional and technical personnel, whether or not they have participated in health lectures related to chronic diseases within 3 years were the influencing factors of the awareness rate of core knowledge. Therefore, the breakthrough point of influencing factors should be strengthened in the future.