Elimination of stubborn organic micropollutants from water is crucial for bioaccumulation prevention and ecosystem protection. Cold plasma activation technology is a clean, sustainable, and highly effective approach to the degradation of micropollutants and pathogens in contaminated water. In this study, we focus on understanding the processes of simultaneous degradation of multiple micropollutants (8 types at maximum) in flowing water by the recently developed microbubble-enhanced cold plasma activation (MB-CPA) technology. The degradation of micropollutants with the treatment time was analyzed by using ultrahigh performance liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-QQQ-MS). We found that the degradation efficiencies of all compounds increase rapidly under strong activation conditions that can lead to above 98% removal of a model compound. After long treatment duration or at a fast flow rate, the removal efficiency was sufficiently high for all compounds that were either easy or hard to degrade. The large variation in degradation efficiencies was present under mild activation conditions. The electron spinning resonance measurements reveal a greater abundance of hydroxyl radicals in treated synthetic river water than pure water, highlighting the effects of water matrix on the degradation efficiency. The understanding from this work may help to design the activation process and minimize the energy consumption for the simultaneous elimination of pollutants in diverse and complex water bodies by cold plasma technology.