Degradation kinetics of antibiotics neomycin and streptomycin was explored spectrophotometrically via their oxidation by cerium(IV) in both sulphuric and perchloric acids. The oxidation reactions demonstrated a 1:8 stoichiometry (antibiotic:cerium(IV)). The kinetics of the reactions in the examined acidic media was first-order with respect to [cerium(IV)] and fractional-first orders with respect to examined antibiotics and H+ concentrations. In the perchloric acid solution, the oxidation reactions of both antibiotics manifested fractional-first-order credence in [H+], whereas the reactions that occurred in sulphuric acid solutions displayed negative less than unit order rate with [H+]. Additionally, different behaviours of the reactions in dissimilar acidic media regarding the influence of ionic strength were recorded. Tests for free radical involvement throughout the oxidation reactions were positive. Under the same circumstances, the rates of neomycin oxidation in both acidic media were lower than those of streptomycin, and those obtained in perchloric acid were higher than those of sulphuric acid for both antibiotic substrates. Conceivable oxidation mechanisms in both sulphuric and perchloric acids consistent with the obtained kinetic results were anticipated. Additionally, the derived rate-law expressions in both acids were in good accordance with the obtained kinetic results. The activation parameters of the oxidation reactions in the acidic media were assessed and debated.