Ciprofloxacin (CIP) is a kind of widely used fluoroquinolone antibiotic, and the widespread presence of CIP in aquatic environment has become a serious issue. Mechanochemical treatment (MCT), as an effective approach to degrade persistent organic pollutants, has many advantages of low-cost, simplicity, and environmentally innocuous. However, few attentions have been paid on employing MCT to treat effluents containing CIP. In this study, MCT was introduced to degrade CIP in aquatic solutions. A series of CIP degradation experiments were conducted by a planetary ball mill, and the influences of main parameters on CIP degradation efficiency were investigated. Furthermore, an optimum combination was selected through orthogonal experiments, and CIP degradation efficiency could reach as high as 99% in certain conditions. Besides, the biotoxicity of CIP solution was also studied. MCT exhibits satisfying performances for degrading CIP in solutions, which make MCT as a promising approach to CIP elimination and also encourages further applications in treating effluents containing other organic pollutants.