For a novel approach of resource-efficient water reuse, a municipal wastewater treatment plant was extended at pilot scale for advanced wastewater treatment, i.e., ozonation and biological activated carbon filtration, and a hydroponic system for reclaimed water driven lettuce cultivation. The treatment specific wastewater lines with the corresponding lettuce plants, differentiated into roots and shoots, were monitored for priority wastewater micropollutants, i.e., acesulfame (sweetener), caffeine (stimulant), carbamazepine, diclofenac, ibuprofen, sulfamethoxazole with acetyl-sulfamethoxazole (human pharmaceuticals), 1H-benzotriazole, and 4/5-methylbenzotriazole (industrial chemicals). As clearly demonstrated, conventional tertiary treatment could not efficiently clean up wastewater. Removal efficiencies ranged from 3% for carbamazepine to 100% for ibuprofen. The resulting pollution of the hydroponic water lines led to the accumulation of acesulfame, carbamazepine, and diclofenac in lettuce root systems at 32.0, 69.5, and 135 μg kg−1 and in the uptake of acesulfame and carbamazepine into lettuce shoots at 23.4 and 120 μg kg−1 dry weight, respectively. In contrast, both advanced treatment technologies when operating under optimized conditions achieved removal efficiencies of > 90% also for persistent micropollutants. Minimizing the pollution of reclaimed water thus met one relevant need for hydroponic lettuce cultivation. Graphical abstract