TiO2-induced photocatalytic decomposition of methyl orange (MO) and atrazine in aqueous solutions was investigated using a top illumination reactor and LC-MS analysis. TiO2 P25 was determined to be the most favorable catalyst when compared to TiO2 Hombikat or Pt-promoted P25 (0.5% Pt/P25). For all catalysts, a strong substrate specificity was observed when simultaneous decomposition was attempted at neutral pH or acidic conditions: MO decomposition was largely preferred over decomposition of atrazine. For TiO2 P25, several process parameters were varied (catalyst loading, MO initial concentration, pH) to determine that the cause of this observation is preferential adsorption. Atrazine decomposition was no longer inhibited by MO at (i) large catalyst concentrations, (ii) at a low MO over atrazine ration, and (iii) at basic conditions (pH 11). Apparently the surface charge of illuminated TiO2 significantly affects the degradation behavior of contaminants when present in mixtures. Surface specificity is not limited to a combination of MO and atrazine, but for P25, this is also shown to occur in decomposition of a mixture of MO and acid orange (AO), compounds with similarity in molecular structure. Consequences of the results for practical application of photocatalysis for water decontamination are briefly discussed.