The coronavirus pandemic has produced considerable effects on medical and demographic processes worldwide and in Russia in particular. The epidemic process involved a sequence of circulating SARS-CoV-2 virus strains with different mutations and this reflected in registered levels of incidence and mortality against spatial heterogeneity of socioeconomic factors in different RF regions. The aim of this study was to analyze spatial-dynamic heterogeneity of the COVID-19 epidemic process in the RF regions in 2020–2023. We performed retrospective analysis of incidence and mortality at the national and regional levels. The analysis relied on departmental statistical data provided by Rospotrebnadzor as well as public data that described the intensive indicators of the COVID-19 epidemic process and results obtained by sequencing of biomaterial samples to identify COVID-19 in them in 2020–2023. In 2020–2023 we identified five ‘waves’ of the COVID-19 epidemic processes that interchanged sequentially. Within these waves, RF regions reached local peaks in incidence with different speed. According to available data, the highest primary incidence among all the RF regions in 2021–2022 was established in Saint Petersburg (12,821.8 cases and 17,341.2 cases per 100 thousand people); the highest mortality in 2021 was detected in the Tver region (427 cases per 100 thousand people) and in the Arkhangelsk region in 2022 (350.9 cases per 100 thousand people).The greatest number of the RF regions where the incidence due to the disease was higher than its average annual level was established in October, November, December 2021 and February 2022 (51, 68, 51 and 82 RF regions accordingly). The established spatial-dynamic heterogeneity of the epidemic process may indicate that this process can be largely determined by differences in the initial socioeconomic, medical and demographic characteristics of the RF religions. Limitations of the study are related to the used statistical data on registered incidence and mortality as well as the concept of the epidemiological ‘wave’ accepted in it. The identified territorial differences in the COVID-19 epidemic process should be considered when developing optimal regulatory impacts including those aimed at predicting probable emergent infections.