Two dimensional transition metal dichalcogenides as potential catalysts to solve energy and environmental crises have caused significant research interests in recent years. In this work, edge-selectively Fe@3D-WS2 nanoflowers with the abundant single-layer were efficiently prepared by dry ball milling for levofloxacin (LEVO) elimination. Together with the advantages of the single-layer active edges and the stretch of W-S bond, the as prepared Fe@3D-WS2 showed the ultra-high degradation efficiency for LEVO under ball-milling condition. This high degradation activity was demonstrated to be originated from piezo-catalysis, rather than adsorption or thermocatalysis. In addition, the Fe@3D-WS2 also showed an ultra-high reusability during the cyclic tests, which is due to its special "self-renewing" behavior under ball milling condition. The degradation efficiency of the Fe@3D-WS2 still reached (similar to) 99% after ten cyclic tests. Both oxygen radicals (O-1(2), O-2(center dot-)) and center dot OH radicals were generated and took part in the LEVO degradation, while oxygen radicals were more contributed to the LEVO degradation. The present work not only provides an important insight for designing efficient catalysts, but also extends the possible application areas of ball milling technique.