Abstract: Objective To analyze the mortality levels and trends of four major chronic non-communicable diseases (hereinafter referred to as chronic diseases) among Chinese residents from 2013 to 2021, and to provide a scientific basis for the formulation of more precise and effective chronic disease prevention and control strategies and more targeted medical resource allocation. Methods The mortality data of the four major chronic diseases (malignant tumors, diabetes mellitus, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases) in China from 2013 to 2021 were obtained from the China Cause of Death Surveillance (CCDS) dataset. Joinpoint 5.2.0 was used for stratified analysis of the data for the changing trends in crude mortality rates (CMRs) and standardized mortality ratios (SMRs) of the four chronic diseases among Chinese residents by gender and region. Meanwhile, the average annual percentage change (AAPC) were also calculated. Results In 2021, the CMRs of malignant tumors, diabetes mellitus, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases were 164.20/100 000, 18.88/100 000, 353.31/100 000, and 52.58/100 000, respectively, totaling 588.97/100 000; the SMRs were 112.64/100 000, 12.37/100 000, 221.32/100 000, and 31.77/100 000, respectively, totaling 380.89/100 000. From 2013 to 2021, the AAPCs for the CMRs of the above four chronic diseases were 1.03%, 5.79%, 2.61%, and -4.10%, respectively, totaling 1.36%; the AAPCs for the SMRs of the above four chronic diseases were -2.38%, 2.51%, -1.31%, and -8.30%, respectively, totaling -1.50%. When analyzed by gender and region (urban and rural areas), the changing trends in the SMRs of the four major chronic diseases from 2013 to 2021 were consistent with those of the total population, with males showing higher values than females in SMRs of malignant tumors, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases, as well as the pooled SMR of the four major chronic diseases, but lower values than females in the SMR of diabetes mellitus from 2013 to 2016. The SMRs of malignant tumors in urban areas were higher than those in rural areas from 2014 to 2018, and the SMR of diabetes mellitus was higher than that in rural areas, while the SMRs of cardiovascular and cerebrovascular diseases and chronic respiratory diseases and the pooled SMRs of the four chronic diseases were lower than those in rural areas. Conclusion From 2013 to 2021, the prevention and control of chronic diseases have yielded positive outcomes, with the reduced SMRs of malignant tumors, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases. However, the CMR and SMR of cardiovascular and cerebrovascular diseases remained at a relatively high level, and the CMR and SMR of diabetes mellitus showed an increasing trend. These findings necessitate greater efforts in the prevention and control of cardiovascular and cerebrovascular diseases and diabetes mellitus in key populations.