“Blue energy” technologies such as reverse electrodialysis (RED) have received significant research attention over the last several years as a means of generating clean electricity from natural salinity gradients (e.g., seawater and river water). To date, however, knowledge of RED is largely based on synthetic sodium chloride solutions that simulate natural waters. Accordingly, in this work we measured the RED performance of five real water pairs, including seawater, river water, desalination brine, saline wastewater from a pickling plant, and treated wastewater. We compared the performance of each real water pair with that of synthetic control waters to investigate the individual impacts of inorganic constituents (e.g., multivalent ions) and natural organic matter (NOM). Our results indicate that the presence of NOM has a larger impact on power density than ionic composition. Specifically, NOM reduced power densities by up to 43%, while inorganic constituents reduced power densities by up to 8% compared to control waters. Furthermore, UV-absorbing NOM present in the dilute compartment of the RED stack was strongly associated with reduced membrane permselectivity and energy efficiency. Taken together, our findings highlight the important role of organic matter in determining the RED performance of real waters.