In order to understand true incident burden of epilepsy in South America and Caribbean, several sources were searched in multiple languages using keywords and combinations. The results were presented as counts, proportions, means, and/or medians along with their 95% confidence intervals (CI). No information was found from Caribbean and no information was available from six South American countries. Based on 14 estimates, annual median incidence (N = 185319, 1984–2010, 7 in rural area) of epilepsy for South America was 115.2/100,000 (95% CI 61.0–133.4, range 0.0–410.0). Random-effect pooled annual epilepsy incidence was 84.8/100,000 (95% CI 65.2–104.5). The 25th and 75th percentile of annual epilepsy incidence were 62.2/100,000 and 130.9/100,000 respectively with an interquartile range (IQR) of 68.7. Between-study variance attributable to each explanatory factor was estimated to be: 38.8% from study year, 18.1% from urban-rural milieu, 15.4% from case size, and 0.6% from study size. Descriptively, on average, 445824 (between 236070 and 516258) new cases of epilepsy are possibly occurring every year in South America. In conclusion, Caribbean needs to come forward for its own epilepsy incidence data especially when risk from numerous factors such as substance abuse, mental health, etc. deems high. Epilepsy incidence in South America is likely to be slightly lower than previously reported although this varies considerably for each country. Inter-population differences are in-part (more than 50%) related to urban-rural differences and variations over time. Our work is especially important to monitor secular trends of epilepsy incidence especially when new data would emerge and countries continue to undergo transitions.