The column dynamics of simple ion-exchange processes involving acetic acid and N-acetylmethionine were studied using a strong-base anion exchange resin to reveal the complex relation between pH, concentration, equilibrium isotherms, and chromatographic separation in ion-exchange chromatography of weak electrolytes. Changing either the influent pH or the concentration, while keeping the other variable constant, led to considerable effluent concentration and pH-fluctuations, respectively. This behavior is caused mainly by the uptake of undissociated acids. To describe these phenomena quantitatively, a rigorous thermodynamics-based equilibrium model for ion exchange, including Donnan potential and reaction equilibria, was incorporated into a fixed-bed model. Experimental results can be described well by this dynamic model, which is superior to conventional models due to its explicit incorporation of colons and partitioning of neutral species. It has great potential for optimizing chromatographic separations of weak electrolyte solutions.