Biochar from spent malt rootlets was employed as the template to synthesize hybrid biochar-ceria materials through a wet impregnation method. The materials were tested for the activation of persulfate (SPS) and subsequent degradation of sulfamethoxazole (SMX), a representative antibiotic, in various matrices. Different calcination temperatures in the range 300–500 °C were employed and the resulting materials were characterized by means of N2 adsorption and potentiometric mass titration as well as TGA, XRD, SEM, FTIR, DRS, and Raman spectroscopy. Calcination temperature affects the biochar content and the physicochemical properties of the hybrid materials, which were tested for the degradation of 500 μg L−1 SMX with SPS (in the range 200–500 mg L−1) in various matrices including ultrapure water (UPW), bottled water, wastewater, and UPW spiked with bicarbonate, chloride, or humic acid. Materials calcined at 300–350 °C, with a surface area of ca. 120 m2 g−1, were the most active, yielding ca. 65% SMX degradation after 120 min of reaction in UPW; materials calcined at higher temperatures as well as bare biochar were less active. Degradation decreased with increasing matrix complexity due to the interactions amongst the surface, the contaminant, and the oxidant. Experiments in the presence of scavengers (i.e., methanol, t-butanol, and sodium azide) revealed that sulfate and hydroxyl radicals as well as singlet oxygen were the main oxidative species.