Dengue fever (DF) has been a growing public-health concern in China since its emergence in Guangdong Province in 1978. Of all the regions that have experienced dengue outbreaks in mainland China, the city of Guangzhou is the most affected. This study aims to investigate the potential risk factors for dengue virus (DENV) transmission in Guangzhou, China, from 2006 to 2014. The impact of risk factors on DENV transmission was qualified by the q-values calculated using a novel spatial-temporal method, the GeoDetector model. Both climatic and socioeconomic factors were considered. The impacts on DF incidence of each single factor and the interaction of two factors were analysed. The results show that the number of days with rainfall of the month before last has the highest determinant power, with a q-value of 0.898 (P < 0.01); the q-values of the other factors related to temperature and precipitation were around 0.38–0.50. Integrating a Pearson correlation analysis, nonlinear associations were found between the DF incidence in Guangzhou and the climatic factors considered. The coupled impact of the different variables considered was enhanced compared with their individual effects. In addition, an increased number of tourists in the city were associated with a high incidence of DF. This study demonstrates that the number of rain days in a month has great influence on the DF incidence of the month after next; the temperature and precipitation have nonlinear impacts on the DF incidence in Guangzhou; both the domestic and overseas tourists coming to the city increase the risk of DENV transmission. These findings are useful in the risk assessment of DENV transmission, to predict DF outbreaks and to implement preventive DF reduction strategies.