The photochemistry of organic contaminants present in ice is receiving growing attention, given the wide presence of ice during winter in temperate regions as well as Polar and mountain environments. Differences between ice photochemistry and aqueous photochemistry, however, influence the quantitative fate and transformation of organic chemicals present in freshwater, marine and ice-cap environments and these differences need to be explored. Here we comparatively studied the ice and aqueous photochemistry of three antibiotics levofloxacin (LVX), sulfamerazine (SM), and chlortetracycline (CTC) under the same simulated sunlight (λ > 290 nm). Their photodegradation in ice/water followed pseudo-first-order kinetics, whereby the photolytic rates of LVX in ice and water were found to be similar, SM photodegraded faster in ice, while CTC underwent slower photodegradation in ice. Whether individual antibiotics underwent faster photodegradation in ice or not depends on the specific concentration effect and cage effect coexisting in the ice compartment. In most cases, the fastest photodegradation occurred in freshwater ice or in fresh water, and the slowest photolysis occurred in pure-water ice or in pure water. This can be attributed to the effects of key photochemical reactive constituents of Cl−, HA, NO3− and Fe(III), that exist in natural waters. These constituents at certain levels showed significant effects (P < 0.1) on the photolysis, not only in ice but also in water. However, these individual constituents at a given concentration, serve to either enhance or suppress the photoreaction, depending on the specific antibiotic and the matrix type (e.g., ice or aqueous solution). Furthermore, extrapolation of the laboratory findings to cold environments indicate that pharmaceuticals present in ice will have a different photofate compared to water. These results are of particular relevance for those regions that experience seasonal ice cover in fresh water and coastal marine systems. Environmental photochemistry of antibiotics in ice and in water. Display omitted •It is a detailed comparison of the ice and aqueous photochemistry of antibiotics.•Similarities and differences of the photodegradation in ice and in water are revealed.•The order of photodegradation rates differs in the two phases of different waters.•Reaction matrix and water constituents have an obvious impact on photolytic kinetics.•Photochemical fate of antibiotics depends on the reaction media, latitudes and seasons.