Dengue fever is a mosquito-borne viral disease caused by the dengue virus of the Flaviviridae family and is responsible for colossal health and economic burden worldwide. This study aimed to investigate the effect of environmental, seasonal, and spatial variations on the spread of dengue fever in Sri Lanka. The study used secondary data of monthly dengue infection and the monthly average of environmental parameters of 26 Sri Lankan regions from January 2015 to December 2019. Besides the descriptive measurements, Kendall's tau_b, Spearman's rho, and Kruskal-Wallis H test have been performed as bivariate analyses. The multivariate generalized linear negative binomial regression model was applied to determine the impacts of meteorological factors on dengue transmission. The aggregate negative binomial regression model disclosed that precipitation (odds ratio: 0.97, p < 0.05), humidity (odds ratio: 1.05, p < 0.01), and air pressure (odds ratio: 1.46, p < 0.01) were significantly influenced the spread of dengue fever in Sri Lanka. The bioclimatic zone is the vital factor that substantially affects the dengue infection, and the wet zone (odds ratio: 6.41, p < 0.05) was more at-risk than the dry zone. The climate season significantly influenced dengue fever transmission, and a higher infection rate was found (odds ratio: 1.46, p < 0.01) in the northeast monsoon season. The findings of this study facilitate policymakers to improve the existing dengue control strategies focusing on the meteorological condition in the local as well as global perspectives.