The El Niño Southern Oscillation (ENSO) is an oceanic-atmospheric phenomenon influencing worldwide weather and climate. Its occurrence is determined by the sea surface temperature (SST) anomaly of the 3.4 Niño region in the Pacific Ocean (5°N-5°S, 120°-170°W). El Niño (EN), Neutral (NT), and La Niña (LN) are the three possible phases of ENSO, respectively for warm, normal, and cold SST anomaly. As in other regions around the world, weather in Brazil is influenced by ENSO phases. The country is the major coffee producer in the world and production is strongly influenced by weather conditions, which affect plant yield, harvest quality, and interactions with pests and diseases. Coffee leaf rust (CLR), caused by the fungus Hemileia vastatrix, is a major cause of coffee yield and quality losses in Brazil, and requires fungicide spray applications every season. Because CLR is highly influenced by weather conditions, it is possible to use weather variables to simulate its progress during the cropping cycle. Therefore, the aims of this study were to estimate CLR infection rate based on a validated empirical model, which has daily minimum air temperature and relative humidity as inputs, and to assess the extent of ENSO influence on the annual risk of this disease at 45 sites in Brazil. Cumulative infection rates (CIR) were estimated daily from October to June of each growing season and location, based on the prevailing ENSO phase. Differences between the extreme phases (EN-LN), were assessed by the Two-One-Sided-Tests (TOST) method. Analysis of data from eight sites, located mainly in Paraná state, provided evidence of CIR differences between EN and LN phases (G1). Evidence of no difference of CIR between EN and LN was found in 18 sites (G2), whereas 19 sites showed no evidence of differences (G3), due to relatively large variation of CIR within the same ENSO phase. The G1 sites are located mostly in Southern Brazil, where ENSO exerts a well-defined influence on rainfall regime. In contrast, the G2 sites are mainly in Minas Gerais state, which is characterized as a transition region for ENSO influence on rainfall. The G3 sites are located between the northern region of Minas Gerais state and southern region of Bahia state, which is characterized by a sub-humid climate that is usually very dry during winter, and where rainfall can vary up to 300% from one year to another, influencing relative humidity and resulting in a high CIR variability. Therefore, ENSO had a well-defined influence on CIR only in Paraná state, a region with minor importance for coffee production in Brazil. No ENSO influence was found in more northerly zones where the majority of Brazilian coffee is produced. This is the first evidence of ENSO-linked regional impact on the risk of coffee rust.