Many previous studies of the impact of oceanic environmental factors on chlorophyll (CHL) in a specific region focused on sea surface temperature (SST), mixed-layer depth (MLD), or wind stress (WS) alone. In this study, relationship between CHL and all those environmental factors (SST, MLD, and WS) in the open ocean was quantified for five regions within the subtropical gyres and the variation trend of 13-year (2003–2015) was analyzed using satellite observations and Argo measurements. The correlation analysis results show that MLD was correlated positively with CHL, SST was correlated negatively with CHL, and the correlation between CHL and WS was either positive or negative. Based on the significance of the correlations, models representing the relationships were established using the multiple linear regression and analyzed, showing that the environmental factors were the major determinants of CHL change. The regression coefficients show that both SST and MLD have remarkable effect on CHL. Our derived models could be used to diagnose the past changes, understand present variability, and predict the future state of CHL changes based on environmental factors, and help us understand the dynamics of CHL variation in the open ocean.