Research assessing the changing epidemiology of infectious diseases in China after the implementation of new healthcare reform in 2009 was scarce. We aimed to get the latest trends and disparities of national notifiable infectious diseases by age, sex, province, and season in China from 2010 to 2019. The number of incident cases and deaths, incidence rate, and mortality of 44 national notifiable infectious diseases by sex, age groups, and provincial regions from 2010 to 2019 were extracted from the China Information System for Disease Control and Prevention and official reports and divided into six kinds of infectious diseases by transmission routes and three classes (A-C) in this descriptive study. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends of incidence and mortality rate. We calculated the concentration index to measure economic-related inequality. Segmented interrupted time-series analysis was used to estimate the impact of the COVID-19 pandemic on the epidemic of notifiable infectious diseases. The trend of incidence rate on six kinds of infectious diseases by transmission routes was stable, while only mortality of sexual, blood-borne, and mother-to-child-borne infectious diseases increased from 0.6466 per 100 000 population in 2010 to 1.5499 per 100 000 population in 2019 by 8.76% per year (95% confidence interval [CI]: 6.88-10.68). There was a decreasing trend of incidence rate on Class-A infectious diseases (EAPC = -16.30%; 95% CI: -27.93 to -2.79) and Class-B infectious diseases (EAPC = -1.05%; 95% CI: -1.56 to -0.54), while an increasing trend on Class-C infectious diseases (EAPC = 6.22%; 95% CI: 2.13-10.48). For mortality, there was a decreasing trend on Class-C infectious diseases (EAPC = -14.76%; 95% CI: -23.46 to -5.07), and an increasing trend on Class-B infectious diseases (EAPC = 4.56%; 95% CI: 2.44-6.72). In 2019, the infectious diseases with the highest incidence rate and mortality were respiratory diseases (340.95 per 100 000 population), and sexual, blood-borne, and mother-to-child-borne infectious diseases (1.5459 per 100 000 population), respectively. The greatest increasing trend of incidence rate was observed in seasonal influenza, from 4.83 per 100 000 population in 2010 to 253.36 per 100 000 population in 2019 by 45.16% per year (95% CI: 29.81-62.33), especially among females and children aged 0-4 years old. The top disease with the highest mortality was still AIDs, which had the highest average yearly mortality in 24 provinces from 2010 to 2019, and its incidence rate (EAPC = 14.99%; 95% CI: 8.75-21.59) and mortality (EAPC = 9.65; 95%CI: 7.71-11.63) both increased from 2010 to 2019, especially among people aged 44-59 years old and 60 or older. Male incidence rate and mortality were higher than females each year from 2010 to 2018 on 29 and 10 infectious diseases, respectively. Additionally, sex differences in the incidence and mortality of AIDS were becoming larger. The curve lay above the equality line, with the negative value of the concentration index, which indicated that economic-related health disparities exist in the distribution of incidence rate and mortality of respiratory diseases (incidence rate: the concentration index = -0.063, p < 0.0001; mortality: the concentration index = -0.131, p < 0.001), sexual, blood-borne, and mother-to-child-borne infectious diseases (incidence rate: the concentration index = -0.039, p = 0.0192; mortality: the concentration index = -0.207, p < 0.0001), and the inequality disadvantageous to the poor (pro-rich). Respiratory diseases (Dec-Jan), intestinal diseases (May-Jul), zoonotic infectious diseases (Mar-Jul), and vector-borne infectious diseases (Sep-Oct) had distinct seasonal epidemic patterns. In addition, segmented interrupted time-series analyses showed that, after adjusting for potential seasonality, autocorrelation, GDP per capita, number of primary medical institutions, and other factors, there was no significant impact of COVID-19 epidemic on the monthly incidence rate of six kinds of infectious diseases by transmission routes from 2018 to 2020 (all p > 0.05). The incidence rates of six kinds of infectious diseases were stable in the past decade, and incidence rates of Class-A and Class-B infectious diseases were decreasing because of comprehensive prevention and control measures and a strengthened health system after the implementation of the new healthcare reform in China since 2009. However, age, gender, regional, and economic disparities were still observed. Concerted efforts are needed to reduce the impact of seasonal influenza (especially among children aged 0-4 years old) and the mortality of AIDs (especially among people aged 44-59 years old and 60 or older). More attention should be paid to the disparities in the burden of infectious diseases.