Since its initial detection in Brazil in February 2020, SARS-CoV-2 and the associated COVID-19 pandemic have continued to devastate Latin America. Specific comorbidities, as well as sociodemographic and lifestyle factors that may be more prevalent in underserved areas, have been identified as risk factors for COVID-19 infection or associated adverse outcomes. Dynamics of infections and deaths in Latin America have varied by country and temporally, as has SARS-CoV-2 variant prevalence; however, more recently, the Delta and subsequent Omicron variants have become ubiquitous. Successful pandemic responses have involved robust infection mitigation measures, testing, and smart deployment of healthcare resourcing. While in some Latin American countries up to 90% of the population is fully vaccinated (i.e., 2 doses) against COVID-19, other countries have failed to reach the World Health Organization’s 70% target. Continued focus on comprehensive surveillance, strategies to maximize vaccine availability and uptake, and mitigation of collateral damage on other aspects of public health and social services are critical for managing the COVID-19 pandemic. This review summarizes the COVID-19 experience in Latin America, including epidemiology and vaccination. Key learnings and future considerations for the ongoing pandemic response are also discussed.