Developing green and efficient advanced oxidation technologies is crucial for removing antibiotics from contaminated water environments. Herein, we employed ozone oxidation to eliminate tetracycline from the water. It was found that ozone micronano bubbles, with a diameter of 0.2−60 μm, exhibited remarkable effectiveness, removing approximately 90% of tetracycline (10 mM) within a mere 20 min. This efficiency was 2.2 times higher than that achieved by larger ozone bubbles with diameters ranging from 0.5 to 4.5 mm. Notably, the ozone micronano bubbles demonstrated a consistent (85%) tetracycline removal rate across a wide pH range (3−11) and in the presence of anions. This remarkable ability to resist environmental interference can be attributed to the high mass transfer efficiency of ozone during the reaction and the production of a large number of reactive oxygen species (ROS). This discovery has been validated through electron paramagnetic resonance (EPR). Furthermore, high-performance liquid chromatography−mass spectrometry (HPLC−MS) spectrum analysis unveiled the tetracycline degradation pathway. In terms of environmental safety, toxicity assessments indicated that most of the resulting byproducts exhibited low toxicity. This work underscores the promising potential of ozone micronano bubbles as an environmentally friendly approach for removing antibiotic contamination from aquatic environment.