Organic fouling plagues many environmental membrane processes. In this study, well-controlled laboratory experiments were performed to elucidate seawater RO membrane fouling by alginic acid. Interfacial free energies derived from multiple probe liquid contact angle analyses (including different seawater matrices) correlated strongly with the rates of membrane fouling. More importantly, the Lewis acid-base interfacial free energy quantitatively described the impacts of calcium-carboxylate complex formation and predicted membrane fouling and cleaning behavior. Calcium ions made polyamide composite RO membranes (and alginic acid) more hydrophobic, enhanced the rate and extent of flux decline, and reduced the effectiveness of chemical cleaning. The implications for seawater RO membrane fouling are clear. Selective removal of calcium ions via pretreatment can reduce the gel forming ability of carboxylate rich biomacromolecules and, hence, the extent to which they foul RO membranes. In addition, RO membranes should be produced with smooth, hydrophilic interfaces comprising monopolar electron-donor functionality and no carboxylic acid residue. More broadly, this paper presents a facile approach for quantifying the impacts of specific ion interactions on aquatic colloid stability, aggregation, and deposition.