Surveillance of meningococcal disease (MD) is crucial after the implementation of vaccination strategies to monitor their impact on disease burden. Adolescent vaccination could provide direct and indirect protection. Argentina, Brazil, and Chile have introduced meningococcal conjugate vaccines (MCV) into their National Immunization Programs (NIP), while Uruguay has not. Here, we analyze the epidemiology of MD and vaccination experience from these four South American countries to identify needs and plans to improve the current vaccination programs. Methodology: Descriptive study of MD incidence rates, serogroup distribution, case fatality rates (CFR), and MCV uptakes during the period 2010-2021 in Argentina, Brazil, Chile, and Uruguay. Data were extracted from national surveillance programs, reference laboratories, NIPs, and Pubmed. Results: MD overall incidence from 2010 to 2021 have a decreasing trend in Argentina (0.37 [IQR = 0.20-0.61]), Brazil (0.59 [IQR = 0.54-1.22]), and Chile (0.45 [IQR = 0.40-0.77]), while a significant increase in Uruguay (0.47 [IQR = 0.33-0.69]) was found from 2016 to 2019. During the COVID-19 pandemic, all countries sharply reduced their MD incidence. The highest incidence rates were observed among infants, followed by children 1-4 years of age. No second peak was evident in adolescents. A reduction in serogroup C, W, and Y cases has occurred in Argentina, Brazil, and Chile after introduction of MCV, serogroup B becoming predominant in all four countries. Median CFR was 9.0%, 21%, 19.9%, and 17.9% in Argentina, Brazil, Chile, and Uruguay, respectively. Median uptake of MCV for Argentina and Brazil were 66.6% and 91.0% for priming in infants; 54.7% and 84.5% for booster in toddlers; and 47.5% and 53% for adolescents; while for Chile, 95.6% for toddlers. Conclusions: Experience after the implementation of MCV programs in South America was successful, reducing the burden of MD due to the vaccine serogroups. High vaccine uptake and the inclusion of adolescents will be crucial in the post-pandemic period to maintain the protection of the population. The increase in the proportion of serogroup B cases emphasizes the importance of continuous surveillance to guide future vaccination strategies.