In a previous study, photonic-based molecularly imprinted polymers (MIPs) were fabricated using atrazine (ATZ) and its metabolites, desethylatrazine (DEA) and desisopropylatrazine (DIA), as templates in separate matrices. For the purposes of monitoring the abovementioned molecules in natural waters, the effect of natural waters—featuring ionic strength and natural organic matter (NOM) on atrazine MIP—were studied in this work, and the photonic MIP was implemented for monitoring the target molecules in natural water samples collected from land in nearby farms in northeast of Columbia MO. Non-imprinted polymers (NIP) were also fabricated and applied in the experiments as a control test. In presence of NaCl, CaCl2 , and NOM, MIPs presented lower responses by 26%, higher responses by 23%, and higher responses by 35%, respectively. NIPs response in terms of an increase or decrease was consistent with those of MIPs, but only for a lower percentage. MIPs response in natural waters—which were characterized for their physicochemical characteristics such as conductivity, total organic carbon content, etc.—provided a good approximation of the real concentrations obtained from the LCMS instrument; in general, they showed a good concordance, although large discrepancies occurred for some samples, which can be related to reproducibility issues in the manufacturing process or the presence of unknown interfering compounds in the real samples.