Leprosy, a chronic infectious disease caused mainly by Mycobacterium leprae (M. leprae), is still an important public health problem in countries such as Brazil and India. Here, we estimate key epidemiological parameters in the Prata Village, a unique, hyper-endemic, former leprosy colony isolated in the Brazilian Amazon. This is a population-based study in which the entire Prata Village population has been enrolled. Clinical, socioeconomic, and demographic data were obtained and validated by cross-checking using three independent information sources. Validated data was used for descriptive epidemiological analysis. From a total of 2,005 inhabitants by the time of the enrollment, 1,084 (56.2%) were born in the Village and, therefore, likely under lifelong exposure to leprosy cases. We observed differences between the sub-populations born and not born in the village in the cumulative prevalence of leprosy (5.9% vs. 22.9%, respectively) and the median age at diagnosis (15 years vs. 28 years, respectively). In contrast, there was no difference in the distribution of cases between males and females. Although extrapolating our findings to more open populations must be done carefully, we believe we used a unique population as a model to provide additional insights into the epidemiology of leprosy.