A continuous 2D ion exchange/RP CEC system was constructed in this report and retention characteristics of weak monoprotic acids in the column were investigated theoretically. The transport equations were deduced for predicting migration behavior of weak monoportic acids based on mixing model combining ion exchange, RP, and electrophoretic separation mechanism. The influences of separation voltage, length of capillary, pH value, and ionic strength of buffer and concentration of organic modifier in mobile phase on the separation were well described by the equations. It was verified that the migration rate of solute was linearly related to voltage in the case of lower voltage, decreased with the increase of the first-dimensional length, and [H+]. The retention time of solute increased with enhancing ionic strength and concentration of organic modifier. These theoretical results were all demonstrated by the relevant experiments. The relevant application was performed for the aqueous extract of Rhizoma gastrodiae, showing the obvious potential in method development for the analysis of complex samples.