Abstract Background Leptospirosis is a zoonotic disease that is considered an important public health problem in tropical regions and the world's poorest countries. Methods In this ecological study, we included cases of leptospirosis reported in Ecuador from 2013 to 2018. Spatial autocorrelation was evaluated through the global Moran I index and spatial-temporal scan statistics were used to identify high-risk clusters. Results In Ecuador, the leptospirosis incidence rates decreased from 3.3 cases per 100 000 population in 2013 to 0.8 cases per 100 000 population in 2018. The global Moran I index for the study period showed a positive spatial autocorrelation (0.68; p=0.001). We identified three significant spatial-temporal clusters for a high occurrence of leptospirosis incidence located in cantons of the Coast and Amazon regions. Conclusions The clusters identified could be targeted by policymakers and stakeholders in order to direct surveillance and understand the dynamics of the distribution of leptospirosis in Ecuador.