Molecular genotyping of Mycobacterium tuberculosis allows for the identification of circulating lineages and sublineages in the population and their relationship with migratory movements. The purpose of this review is to describe the phylogeography of Mycobacterium tuberculosis reported in South American countries that was analyzed using genotyping tools, analyze the Tuberculosis hotspots for the region and determine the impact of the COVID-19 pandemic on the Tuberculosis control program. The Latin American Mediterranean (LAM) sublineage belonging to the Euro-American lineage (Lineage 4) presents the highest prevalence in South America and is followed by the Beijing sublineage belonging to the East Asian lineage (Lineage 2). The Beijing sublineage is considered of worldwide interest because of its association with multidrug-resistant tuberculosis (MDR-TB), which is almost entirely distributed in South America, with Peru being the country with the highest prevalence for this sublineage. On the other hand, the Indo-Oceanic (Lineage 1), India-East Asia (Lineage 3) and West- African 2 (Lineage 6) sublineages have been reported with lower prevalence in South America. The molecular techniques used in the genotyping studies for Mycobacterium tuberculosis in South America were as follows: typing by complementary oligonucleotide spacer sequences (Spoligotyping), restriction-hybridization patterns (IS6110-RFLP, PGRS-RFLP), mycobacterial interspaced repeat units-variable number tandem repeats (MIRU-VNTR) and whole genome sequencing (WGS). At present, Brazil and Peru are the hotspots for tuberculosis and MDR-TB in South America, where the control of tuberculosis wholly affected by the COVID-19 pandemic. Thus, there have been significant impacts on containment programs and possible post-pandemic scenarios such that scientific contributions will need to be evaluated and implemented with new strategies for prevention, diagnosis, treatment and control of Tuberculosis.