Advanced oxidation processes (AOPs), such as UV, UV/H2O2 and UV/persulfate, are widely used to remove emerging organic contaminants from wastewater streams. However, knowledge on chemical degradation pathways, reaction kinetics as well as formation and toxicity of key degradates is limited. We investigated the direct photolysis and •OH/SO4•− dominated kinetics, intermediates and toxicity evolution of three ionizable antiviral drugs (ATVs): tenofovir (TFV), didanosine (DDI), and nevirapine (NVP). Their transformation kinetics were found to depend on the dominant protonated states. Under UV–Vis irradiation (λ > 290 nm), TFV and DDI photolyzed the fastest in the cationic forms (H2TFV+ and H2DDI+), whereas NVP exhibited the fastest photodegradation in the anionic forms (NVP−). The anionic forms (TFV− and NVP−) demonstrated the highest reactivities towards •OH in most cases, while the cationic forms (H2DDI+ and H2NVP+) reacted the fastest with SO4•− for most of the ATVs. The dissociation-dependent kinetics can be attributed to the discrepancies in deprotonation degrees, quantum yields, electron densities and coulombic repulsion with SO4•− in their dissociated forms. Based on the key product identification via HPLC-MS/MS, the pathways involved hydroxylation, dehydroxylation, oxidation, reduction, cyclopropyl cleavage, C-N breaking, elimination, cyclization and deamidation reactions, which can be prioritized based on the specific compound and the photochemical process. Furthermore, a bioassay showed the photomodified toxicity of the ATVs to Vibrio fischeri (bioluminescent bacteria) during the three processes, which was also demonstrated by ECOSAR model assessment. Nearly half of the chemical intermediates were demonstrably more toxic than their respective parent ATVs. These results provide new insights into understanding the persistence, fate and hazards associated with applying the UV-assisted AOPs to treat wastewater containing ATVs.