Leptospirosis is a disease usually acquired by humans through water contaminated with the urine of rodents that comes into direct contact with the cutaneous lesions, eyes, or mucous membranes. The disease has an important environmental component associated with climatic conditions and natural disasters, such as floods. We analyzed the relationship between rainfall and temperature and the incidence of leptospirosis in the top 30 municipalities with the highest numbers of cases of the disease in the period of 2007 to 2016. It was an ecological study of the time series of cases of leptospirosis, rainfall, and temperature with lags of 0, 1, 2, 3, and 4 weeks. A multilevel negative binomial regression model was implemented to evaluate the relationship between leptospirosis and both meteorological factors. In the 30 evaluated municipalities during the study period, a total of 5136 cases of leptospirosis were reported. According to the implemented statistical model, there was a positive association between the incidence of leptospirosis and rainfall with a lag of 1 week and a negative association with temperature with a lag of 4 weeks. Our results show the importance of short-term lags in rainfall and temperature for the occurrence of new cases of leptospirosis in Colombia.