Veterinary antibiotics enter the environment through the application of organic fertilizers to cropland. In this study, the aerobic degradation of tylosin, a widely used antibiotic in the production of livestock and poultry, was conducted in water and in soil in an effort to further investigate its environmental fate. Tylosin is a macrolide antibiotic, which consists of four factors (A, B, C, D). Water and soil were sampled at selected times and analyzed for tylosin and its degradation products by high‐performance liquid chromatography (HPLC), with product identification confirmed by HPLC‐mass spectrometry. Tylosin A is degraded with a half‐life of 200 d in the light in water, and the total loss of tylosin A in the dark is 6% of the initial spiked amount during the experimental period. Tylosin C and D are relatively stable except in ultrapure water in the light. Slight increases of tylosin B after two months and formation of two photoreaction isomers of tylosin A were observed under exposure to light. However, tylosin probably would degrade faster if the experimental containers did not prevent ultraviolet transmission. In soil, tylosin A has a dissipation half‐life of 7 d, and tylosin D is slightly more stable, with a dissipation half‐life of 8 d in unsterilized and sterilized soil. Sorption and abiotic degradation are the major factors influencing the loss of tylosin in the environment, and no biotic degradation was observed at the test concentration either in pond water or in an agronomic soil, as determined by comparing dissipation profiles in sterilized and unsterilized conditions.