The occurrence of emerging pharmaceutical contaminants, especially antibiotics in water systems, is an alarming issue and is addressed using advanced oxidation processes (AOPs). In this study, the degradation of tetracycline hydrochloride (TCT) is evaluated and compared using UV and solar light as the source of energy in the presence of semiconductor oxide catalyst ZnO. Further, the effective solar photocatalytic degradation of TCT in distilled water and aquaculture wastewater was deeply investigated. TCT showed a 62% degradation efficiency in deionized water at the laboratory scale, while aquaculture effluent exhibited 87% degradation efficiency with the ZnO catalyst after 60 minutes of solar irradiation. The effect of multiple contaminants such as chloroquine (CLQ) and sulphamethoxazole (SMX) on TCT degradation was also investigated. CLQ inhibited the degradation of TCT, whereas SMX did not. The effective operational parameters, such as pH, irradiation time, photocatalyst dosage, the effect of oxidants, the effect of anions, and TCT concentration, were studied consecutively. The pseudo-first-order kinetic model best fit the experimental results (different tetracycline concentrations). Complete COD removal of TCT concentrations was achieved in deionized (up to 90 mg/L) and aquaculture wastewater. The catalyst was characterized using SEM, TEM, and XRD images. LC-QTOF analysis was used to identify the intermediates formed during the degradation using a mechanistic pathway. The results suggest the possibility of using inexpensive natural, non-renewable solar energy to purify TCT-contaminated real wastewater, thereby enabling the reuse of scarce water resources.