In this study, the removal of microcontaminants (MCs) by the activation of persulfate (PS) with Fe(III)-EDDS under natural solar radiation in a low-cost raceway pond reactor (RPR) was investigated. The primary focus was to evaluate the effect of the Fe(III)-EDDS molar ratio, initial iron concentration, PS concentration, and initial pH on process performance while using sulfamethoxazole (SMX) and carbamazepine (CBZ) as model MCs. The investigation encompassed three different water matrices: natural water, synthetic municipal wastewater treatment plant (MWWTP) secondary effluent, and actual MWWTP secondary effluent. During experiments in natural water, it was found that 0.1 mM Fe(III) at a 1:2 molar ratio and 0.2 mM Fe(III) at a 1:1 molar ratio resulted in the most adequate operational conditions. Further experiments revealed a general decrease in process efficiency due to water matrix effects; however, this could be compensated by increasing the initial PS concentration and decreasing the initial operation pH. For example, the use of 0.2 mM Fe(III) at a 1:1 Fe(III):EDDS molar ratio, with 2 mM PS at pH 6, allowed for an 80% removal of the MCs sum in approximately 20 min, along with a significant decrease in chronic toxicity (Selenatrum Capricornutum) when working with actual waters. Nonetheless, the final experiment, focused on simultaneous MCs removal and wild bacteria inactivation in actual MWWTP secondary effluent, showed only a 1.6–1.8 log reduction of Escherichia coli, total coliforms, and Enterococcus faecalis. As such, further studies about the solar/Fe(III)-EDDS/PS process are needed to explore new strategies that improve its disinfection efficiency.