The atmospheric total water vapor content (TWVC) affects climate change, weather patterns, and radio signal propagation. Recent techniques such as global navigation satellite systems (GNSS) are used to measure TWVC but with either compromised accuracy, temporal resolution, or spatial coverage. This study demonstrates the feasibility of predicting, mapping, and measuring TWVC using spread spectrum (SS) radio signals and software-defined radio (SDR) technology on low Earth-orbiting (LEO) satellites. An intersatellite link (ISL) communication network from a constellation of small satellites is proposed to achieve three-dimensional (3D) mapping of TWVC. However, the calculation of TWVC from satellites in LEO contains contribution from the ionospheric total electron content (TEC). The TWVC and TEC contribution are determined based on the signal propagation time delay and the satellites’ positions in orbit. Since TEC is frequency dependent unlike TWVC, frequency reconfiguration algorithms have been implemented to distinguish TWVC. The novel aspects of this research are the implementation of time stamps to deduce time delay, the unique derivation of TWVC from a constellation setup, the use of algorithms to remotely tune frequencies in real time, and ISL demonstration using SDRs. This mission could contribute to atmospheric science, and the measurements could be incorporated into the global atmospheric databases for climate and weather prediction models.