Dengue fever is an important arboviral disease in many countries. Its incidence has increased during the last decade in central Vietnam. Most dengue studies in Vietnam focused on the northern area (Hanoi) and southern regions but not on central Vietnam. Dengue transmission dynamics and relevant environmental risk factors in central Vietnam are not understood. This study aimed to evaluate spatiotemporal patterns of dengue fever in central Vietnam and effects of climatic factors and abundance of mosquitoes on its transmission. Dengue and mosquito surveillance data were obtained from the Department of Vector Control and Border Quarantine at Nha Trang Pasteur Institute. Geographic Information System and satellite remote sensing techniques were used to perform spatiotemporal analyses and to develop climate models using generalized additive models. During 2005–2018, 230,458 dengue cases were reported in central Vietnam. Da Nang and Khanh Hoa were two major hotspots in the study area. The final models indicated the important role of Indian Ocean Dipole, multivariate El Niño-Southern Oscillation index, and vector index in dengue transmission in both regions. Regional climatic variables and mosquito population may drive dengue transmission in central Vietnam. These findings provide important information for developing an early dengue warning system in central Vietnam.