Introduction: Heterogeneity of amyotrophic lateral sclerosis (ALS) has been suggested in terms of epidemiology, phenotypes and genetics between geographic areas and populations. However, there is limited information in Latin America. We conducted a systematic review that aimed to describe the epidemiology, frequency of genetic mutations, clinical characteristics and survival of ALS patients in this region. Methods: We reviewed Medline, Scopus, Scielo and LILACS databases up to April 2020. The search terms "Amyotrophic Lateral Sclerosis" or "Motor Neuron Disease" were used in combination with the list of Latin American countries from the United Nations. All observational studies were included. A methodological overview was performed using the principles of descriptive epidemiology. Results: Overall, 1364 publications were identified and 36 studies were selected, covering 13 Latin American countries. According to the original reports, ALS occurrence varied among countries with a standardized incidence ranging from 0.3 per 100,000 person-years follow up (PYFU) in Ecuador to 3.6 per 100,000 PYFU in Uruguay. A low proportion of the C9orf72 repeat expansion was reported in Cuba and Brazil. We identified age at onset between 50 and 60 years. Survival time was higher than 40 months in half of the studies. Data from multiethnic populations reported a higher risk of developing ALS in Caucasians compared to admixed and Black populations. Conclusion: This review provides a perspective of ALS variability across Latin America and highlights specific differences when comparing to Europe and North America. However, we cannot draw firm conclusions because of different methodological concerns within the studies.