A growing number of studies have linked the incidence of leptospirosis with the occurrence of flood events. Nevertheless, the interaction between flood and leptospirosis has not been extensively studied to understand the influence of flood attributes in inducing new cases. This study reviews leptospirosis cases in relation to multiple flood occurrences in Kerala, India. Leptospirosis data were obtained for three years: 2017 (non-flood year) and two years with flooding—2018 (heavy flooding) and 2019 (moderate flooding). We considered the severity of flood events using the discharge, duration and extent of each flooding event and compared them with the leptospirosis cases. The distribution of cases regarding flood discharge and duration was assessed through descriptive and spatiotemporal analyses, respectively. Furthermore, cluster analyses and spatial regression were completed to ascertain the relationship between flood extent and the postflood cases. This study found that postflood cases of leptospirosis can be associated with flood events in space and time. The total cases in both 2018 and 2019 increased in the post-flood phase, with the increase in 2018 being more evident. Unlike the 2019 flood, the flood of 2018 is a significant spatial indicator for postflood cases. Our study shows that flooding leads to an increase in leptospirosis cases, and there is stronger evidence for increased leptospirosis cases after a heavy flood event than after a moderate flooding event. Flood duration may be the most important factor in determining the increase in leptospirosis infections.