A large outbreak of dengue, with the most documented cases, occurred in Guangdong China in 2014. Epidemiological studies and phylogenetic analysis of the isolated dengue virus (DENV) showed this outbreak was attributed to multiple sources and caused by at least two genotypes of DENV-1 (Genotypes I and III) and two genotypes of DENV-2 (Cosmopolitan and Asian I Genotypes). A retrospective review and phylogenetic analysis of DENV isolated in Guangdong showed that DENV-1 Genotype I strains were reported continuously during 2004-2014, Genotype III strains were reported during 2009-2014 ; DENV-2 Cosmopolitan and Asian I Genotype strains were reported continuously during 2012-2014. At least 45,171 cases were reported in this outbreak, with 65.9% of the patients in the 21-55-year-old group. A trend toward a decrease in the daily newly emerged cases lagged by approximately 20 days compared with the mosquito density curve. Several epidemiological characteristics of this outbreak and the stably sustained serotypes and genotypes of DENV isolated in Guangdong suggest that Guangdong has been facing a threat of transforming from a dengue epidemic area to an endemic area. The high temperature, drenching rain, rapid urbanization, and pandemic of dengue in Southeast Asia may have contributed to this large outbreak of dengue.