Benzothiazole, a high-production chemical used in domestic and industrial applications, possesses a persistent nature and is ubiquitous in aquatic environments; this study aims to investigate benzothiazole degradation by utilizing a UV-activated persulfate process (UV/persulfate). The results demonstrated that the UV/persulfate process can efficiently degrade benzothiazole in deionized water (the pseudo-first-order degradation rate constant (kobs) was 0.0847 min−1 under the experimental conditions of [benzothiazole]0 = 10 mg/L, [persulfate]0 = 150 mg/L and initial solution pH = 7). kobs and persulfate dose (18.75 to 150 mg/L) exhibited a linearly proportional relationship (R2 = 0.9696). The optimal benzothiazole degradation rate occurred at pH 7 (kobs = 0.0847 min−1) compared with those at pH 3 (kobs = 0.0516 min−1) and 11 (kobs = 0.0450 min−1). The presence of common water constituents (HCO3–, Cl–, NO3– and dissolved organic matter) had an inhibitory effect on benzothiazole degradation. Radical scavenger experiments showed that both SO4•– and •OH were involved in benzothiazole degradation, with SO4•– playing a relatively predominant role. The second-order rate constant between SO4•– and benzothiazole was 2.1 × 109 M−1 s−1. Two transformation byproducts of benzothiazole degradation were detected, which were generated through the dihydroxylation and trihydroxylation reactions of benzothiazole. During the UV/persulfate process, the toxicity (Microtox®) increased and then declined within 60 min of reaction time. The results suggested that the UV/persulfate process is an efficient way to remove benzothiazole from water.