It has been argued that the interannual variation of tropical-mean upper tropospheric (UT) water vapor follows the change of temperature, and the latter varies approximately linearly with sea surface temperature (SST). The co-variability of mean water vapor and temperature is seemingly consistent with the “fixed relative humidity” (FRH) assumption. However, the mechanism for the validity of the FRH assumption is not simply determined by the Clausius-Clapeyron equation. Clouds associated deep convection are closely coupled with water vapor variability, especially in the UT. Using simultaneous satellite measurements of UT water vapor, temperature, clouds and SST along with climate model simulations, we examine the relationships between these parameters from local to global (tropical) scale, in order to identify the mechanisms for UT water vapor variability. It is found that enhanced convection corresponds to increased UT water vapor locally and vice versa. Departures of UT relative humidity from the mean based on the FRH assumption can be substantial. When a large-scale average is considered, contributions from difference regions are compensatory, leading to a mean relative humidity more or less “fixed”. The state-of-the-art satellite observations are extremely valuable to quantify the local and global UT water vapor changes.