Many impurities, due to their incomplete biodegradation in wastewater treatment plants, are often detected in surface waters. Bisphenol A, bisphenol S, and fluconazole are the examples used in the present study to show an alternative approach to degradation using UV-activated persulfate, allowing for fast removal of the tested compounds within minutes with no significant reduction in efficiency in a wide pH range. Although the first steps of the process led to degradation products of similar toxicity, further degradation resulted in the formation of compounds of a few orders of magnitude lower toxicity, which is important in reducing the environmental impact of both bisphenols and fluconazole. Elimination of bisphenol A from spiked water solution was achieved in 2 min, and both bisphenol S and fluconazole in 5 min. The developed procedure was also applied to the effluent from a wastewater treatment plant. Effective removal of bisphenol A was noted after 5 min and bisphenol S after 30 min, but no more than about 80% fluconazole was eliminated within 1 h. Nevertheless, despite the lower removal rate compared to water solutions tests, the results were better than when only UV radiation was used to remove the tested compounds. It was confirmed that the process with UV-activated persulfate is considerably faster than the reported thermally-activated one. Furthermore, the proposed process is cost-efficient because the UV irradiation of wastewater treatment plant effluent is often used for disinfection while increasing temperature requires additional energy.