The pandemic caused by COVID-19 has had diverse effects on the population and businesses. Due to their low visibility, there is a significant knowledge gap for the scientific community regarding the situation of South American entrepreneurship during the COVID-19 pandemic. Therefore, this systematic review aims to answer the following research questions: What scientific evidence is available on entrepreneurship in South America during the COVID-19 pandemic? From which countries do the studies originate? What conclusions do they present, and what lessons can be learned from them? The Scopus and Scielo databases were explored in this systematic review. Due to the diversity of languages in which articles from this region are published, searches were conducted in English, Spanish, and Portuguese. In each case, we searched for results containing the words COVID-19 and entrepreneurship (emprendimiento in Spanish, empreendedorismo in Portuguese) in the title, abstract, or keywords. The initial search produced 783 records, which were filtered based on seven criteria, resulting in 15 articles. The final articles identified had corresponding authors affiliated with South American institutions. We conclude that, in South America, some entrepreneurs recognize the importance of maintaining the economic stability of their employees and communities in addition to sustaining their businesses. Their actions serve as case studies of resilience and perseverance in adverse circumstances.