The aim of this study is to compare the removal of organic micropollutants (OMPs) in wastewater by activated sludge (AS) and constructed wetlands (CWs). This analysis was carried out in a wastewater treatment plant (WWTP) of a rural community where they implemented two technologies in parallel: AS and a pilot plant of horizontal subsurface flow (HSSF) constructed wetlands. In this case, these systems were fed by the same influent and the removal efficiencies of 14 OMPs, including analgesics/anti-inflammatories, anticonvulsants, stimulants, antifungals, fragrances, plasticizers, and transformation products, were evaluated in each system. Regarding the presence of OMPs in the wastewater, the concentrations of these compounds in the influent ranged from 0.16 to 7.75 µg/L. In general, the removal efficiencies achieved by the AS system were between 10%–95% higher than those values reported by HSSFs with values above 80% for naproxen, ibuprofen, diclofenac, caffeine, triclosan, methyl dihydrojasmonate, bisphenol-A, 2-hydroxyl ibuprofen, and carboxy ibuprofen (p < 0.05). This behavior can be related to the aerobic conditions that promote the AS system with oxidation-reduction potential (ORP) and dissolved oxygen (DO) values above −281 mV and 0.24 mg/L, respectively. However, the removal of galaxolide was greater in HSSF system than in AS with significant difference of 70% (p < 0.05). Despite these results, this study reveals that comparing both technologies, AS had the best removal performance of these OMPs studied.