Leprosy remains a public health problem in Brazil, and the Mato Grosso do Sul State (MS) had the seventh highest rate of detection of new cases in the country in 2015 (26.59 per 100,000 inhabitants) which was classified as very high. This work aimed to determine the epidemiological characteristics of leprosy in MS. Descriptive statistics were performed with data from the Information System on Diseases of Compulsory Declaration (SINAN) between 2001 and 2015, with all patients included in the system serving as the sample. Clinical forms of multibacillary (MB) leprosy predominated in MS during the study period, with a clear positive trend from 2009 to 2015 and a peak in the detection rate of new cases (NCDR) in 2014 corresponding to 40.39 per 100,000 population (p<0.001). The most affected groups were men (56.7%) aged 20–59 years (70.52%), an economically active population. We observed that Northern MS had the highest overall NCDR in the State. In cities bordering other countries, NCDRs were significantly lower than in those of other analyzed cities. There was no dependency ratio correlating NCDRs in cities with higher or lower indexes with basic care coverage (p=0.799) and human development index (p=0.887). In conclusion, the large number of patients with MB leprosy indicates that the diagnosis of leprosy is delayed in MS, perhaps due to difficulties related to diagnostic methods. This situation contributes to the continuing prevalence of leprosy in MS.