Because industrialization is increasing the number of manufacturing facilities in traditionally rural agricultural areas globally, ground and surface waters with mixed fertilizer and industry contaminants must be considered. This work characterizes the effect of nitrates, phosphates, and chromates on the removal of phosphates and chromates from contaminated water via ion exchange with calcined hydrotalcite, an inexpensive, synthetic double layer hydroxide. Isotherms for single ion removal are compared with those for multi-ion solutions at contaminant levels typical for contaminated ground and surface waters. In addition, fixed effects statistical analysis of variance, PROC GLM (SAS Version 9) was used to analyze main and interactive effects for target anion removal and Least Significance Difference t-test and Tukey’s studentized range honest significant difference at α = 0.05 were used a multiple comparison procedures to determine significant mean difference in treatments. It was found that in a binary phosphate-chromate system, phosphate removal was only significantly reduced by higher chromate levels and this effect was magnified at higher phosphate levels. Chromate removal, on the other hand, was reduced at all phosphate levels. For the ternary system, phosphate removal was reduced by chromates, but not nitrates. However, the chromate-nitrate interaction was significant, as was the ternary interaction, particularly at higher phosphate levels. Chromate removal in the ternary system was impacted by the main effects for chromate, phosphate, and nitrate and also by all of the interactive effects. Hence, a multi-step ion exchange process would be required to remove all anions of concern in a mixed contaminant system.