The aim of this study is to develop a model that correctly identifies and quantifies the relationship between dengue and meteorological factors in Guangzhou, China. By cross-correlation analysis, meteorological variables and their lag effects were determined. According to the epidemic characteristics of dengue in Guangzhou, those statistically significant variables were modeled by a zero-inflated Poisson regression model. The number of dengue cases and minimum temperature at 1-month lag, along with average relative humidity at 0- to 1-month lag were all positively correlated with the prevalence of dengue fever, whereas wind velocity and temperature in the same month along with rainfall at 2 months’ lag showed negative association with dengue incidence. Minimum temperature at 1-month lag and wind velocity in the same month had a greater impact on the dengue epidemic than other variables in Guangzhou.