Photocatalysis is a rapidly expanding technology for wastewater treatment, including a wide range of organic pollutants. Thus, understanding the kinetics and mechanism of the photocatalytic oxidation (PCO) for degradation of phenoxyacetic acid (PAA) is an indispensable component of risk assessment. In this study, we demonstrated that the central composite design (CCD) coupled with response surface methodology (RSM) was successfully employed to probe the kinetics and mechanism of PCO degradation for PAA using an efficient zinc oxide (ZnO) photocatalyst. In our current case study, four independent factors such as ZnO dosage, initial concentration of PAA, solution pH, and reaction time on the PCO degradation for PAA were examined in detail. Based on our results obtained from RSM analyses, an efficient pathway leading to the high degradation rate (>90%) was applying 0.4 g/L of ZnO dosage with 16 mg/L of concentration of PAA at pH 6.73 for 40 minutes. The experimental results were fitted well with the derived response model with R2 = 0.9922. This study offers a cost-effective way for probing our global environmental water pollution issue.