Background: The evidence of increased mortality attributable to extreme temperatures is widely characterized in climate-health studies. However, few of these studies have examined the role of humidity on temperature-mortality association. We investigated the joint effect between temperature and humidity on cardiovascular disease (CVD) mortality in Zhejiang Province, China. Methods: We collected data on daily meteorological and CVD mortality from 11 cities in Zhejiang Province during 2010-2013. We first applied time-series Poisson regression analysis within the framework of distributed lag non-linear models to estimate the city-specific effect of temperature and humidity on CVD mortality, after controlling for temporal trends and potential confounding variables. We then applied a multivariate meta-analytical model to pool the effect estimates in the 11 cities to generate an overall provincial estimate. The joint effects between them were calculated by the attributable fraction (AF). The analyses were further stratified by gender, age group, education level, and location of cities. Results: In total, 120,544 CVD deaths were recorded in this study. The mean values of temperature and humidity were 17.6 °C and 72.3%. The joint effect between low temperature and high humidity had the greatest impact on the CVD death burden over a lag of 0-21 days with a significant AF of 31.36% (95% eCI: 14.79-38.41%), while in a condition of low temperature and low humidity with a significant AF of 16.74% (95% eCI: 0.89, 24.44). The AFs were higher at low temperature and high humidity in different subgroups. When considering the levels of humidity, the AFs were significant at low temperature and high humidity for males, youth, those with a low level of education, and coastal area people. Conclusions: The combination of low temperature and high humidity had the greatest impact on the CVD death burden in Zhejiang Province. This evidence has important implications for developing CVD interventions.