Treated wastewater (TWW) is increasingly used for agricultural irrigation in arid and semiarid areas, but it can introduce contaminants of emerging concern (CECs) into the food chain, posing a potential risk to human health. While many studies have shown that plants can accumulate some CECs, so far little effort has been made to explore mitigation strategies. This study tested the concept of alternating between TWW with conventional freshwater for irrigation to minimize CEC accumulation in plants. Tomato and lettuce seedlings were first cultivated in CEC-containing hydroponic solutions for 3 weeks, and then in CEC-free media for another 3 weeks. The plant tissues contained elevated concentrations of perfluorobutanesulfonate, perfluorobutanoic acid, perfluorohexanoic acid, carbamazepine, and fluoxetine ranging from 42.1 to 2724.2 ng/g (dry weight). However, after being transferred to CEC-free media, most CEC levels decreased by over 75%, attributed to plant metabolism, growth dilution and back release to culture media. This proof-of-concept study suggested that using TWW during the early part of the growing season may effectively minimize CEC accumulation. Such hybrid irrigation schemes have a great prospect for expanding the safe reuse of TWW and other lower-quality water sources in agriculture and should be further evaluated under field conditions.