Pharmaceuticals, especially antibiotics, constitute an important group of aquatic contaminants given their environmental impact. Specifically, tetracycline antibiotics (TCs) are produced in great amounts for the treatment of bacterial infections in both human and veterinary medicine. Several studies have shown that, among all antibiotics, oxytetracycline hydrochloride (OTC HCl) is one of the most frequently detected TCs in soil and surface water. The results of the photocatalytic degradation of OTC HCL in aqueous suspensions (30 mg·L−1) of 0.5 wt.% cobalt-doped TiO2 catalysts are reported in this study. The heterogeneous Co-TiO2 photocatalysts were synthesized by two different solvothermal methods. Evonik Degussa Aevoxide P25 and self-prepared TiO2 modified by the same methods were used for comparison. The synthesized photocatalysts were characterized by X-ray powder diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), UV/vis diffuse reflectance spectroscopy (DRS), and N2 adsorption (BET) for specific surface area determination. The XRD and Raman results suggest that Ti4+ was substituted by Co2+ in the TiO2 crystal structure. Uv/visible spectroscopy of Co-TiO2-R showed a substantial redshift in comparison with bare TiO2-R. The photocatalytic performance of the prepared photocatalysts in OTC HCL degradation was investigated employing Uv/vis spectroscopy and high-performance liquid chromatography (HPLC). The observed initial reaction rate over Co-TiO2-R was higher compared with that of Co-TiO2-HT, self-prepared TiO2, and the commercial P25. The enhanced photocatalytic activity was attributed to the high surface area (153 m2·g−1) along with the impurity levels within the band gap (2.93 eV), promoting the charge separation and improving the charge transfer ability. From these experimental results, it can be concluded that Co-doping under reflux demonstrates better photocatalytic performances than with the hydrothermal treatment.