Epilepsy is the most common major neurological disorder that affects people of all ages. The prevalence varies from one country to another and even between different areas, due to a lack of access to medical care for reasons related to limited resources. Epilepsy is a worldwide public health problem that affects more deeply populations living in developing countries such as Mexico, where more aggressive health policies based on epidemiological data are needed; however, this information is scarce and the evolution of this data over time remains unclear. The aim of the present study is to provide an overview of the epidemiology of epilepsy in Mexico from 1970 to 2020. We searched descriptive epidemiological studies on epilepsy in rural and urban regions of Mexico from 1970 to 2020. Available data on the sociodemographic characteristics, prevalence, and incidence data were extracted. Finally, the abstract, full-text review, and data abstraction were conducted in duplicate and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Descriptive statistics was also used. Overall, 11 underrepresented and heterogeneous epidemiological studies were included. In total, the prevalence of epilepsy in Mexico is 3.9 to 41:1,000 inhabitants; 3.9 to 41 per 1,000 persons in rural regions, and 3.49 to 44.3 per 1,000 persons in urban regions. None of these studies addressed the incidence of epilepsy. The prevalence of epilepsy in Mexico has remained unchanged during the last 5 decades. Our results confirm a high prevalence of epilepsy in both urban and rural settings in Mexico that remain unchanged during the last 5 decades. All studies included in the present review showed multiple methodological limitations. New and robust epidemiological studies are needed to delineate the epidemiological profile of epilepsy in Mexico.