All South American countries from the Southern cone (Argentina, Brazil, Chile, Paraguay and Uruguay) experienced severe COVID-19 epidemic waves during early 2021 driven by the expansion of variants Gamma and Lambda, however, there was an improvement in different epidemic indicators since June 2021. To investigate the impact of national vaccination programs and natural infection on viral transmission in those South American countries, we analyzed the coupling between population mobility and the viral effective reproduction number Rt. Our analyses reveal that population mobility was highly correlated with viral Rt from January to May 2021 in all countries analyzed; but a clear decoupling occurred since May-June 2021, when the rate of viral spread started to be lower than expected from the levels of social interactions. These findings support that populations from the South American Southern cone probably achieved the conditional herd immunity threshold to contain the spread of regional SARS-CoV-2 variants.