Background: China is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time. Objective: This study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020. Methods: We extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen's methods to investigate the diseases' temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality. Results: Between January 2005 and December 2020, 51, 028, 733 incident cases and 261, 851 attributable deaths were recorded. Pertussis (P = .03), dengue fever (P = .01), brucellosis (P = .001), scarlet fever (P = .02), AIDS (P< .001), syphilis (P< .001), hepatitis C (P< .001) and hepatitis E (P = .04) exhibited significant upward trends. Furthermore, measles (P< .001), bacillary and amebic dysentery (P< .001), malaria (P = .04), dengue fever (P = .006), brucellosis (P = .03), and tuberculosis (P = .003) exhibited significant seasonal patterns. We observed marked disease burden-related geographic disparities and heterogeneities. Notably, high-risk areas for various infectious diseases have remained relatively unchanged since 2005. In particular, hemorrhagic fever and brucellosis were largely concentrated in Northeast China; neonatal tetanus, typhoid and paratyphoid, Japanese encephalitis, leptospirosis, and AIDS in Southwest China; BAD in North China; schistosomiasis in Central China; anthrax, tuberculosis, and hepatitis A in Northwest China; rabies in South China; and gonorrhea in East China. However, the geographical distribution of syphilis, scarlet fever, and hepatitis E drifted from coastal to inland provinces during 2005-2020. Conclusions: The overall infectious disease burden in China is declining; however, hepatitis C and E, bacterial infections, and sexually transmitted infections continue to multiply, many of which have spread from coastal to inland provinces.