The presence of antibiotics in the environment causes increasing attention due to their potential risks to ecosystems and public health. Laccases are versatile oxidases capable of degrading various organic contaminants including pharmaceuticals. However, the performance of bacterial laccases on tetracycline antibiotics (TCs) degradation is seldom investigated. In this work, a bacterial laccase from Bacillus amyloliquefaciens was immobilized as laccase-inorganic hybrid nanoflowers (Lac-hNFs) by a facile and rapid method. The immobilized laccase was employed to remove different TCs including tigecycline, which is a third-generation TC that its degradation by laccase has not been reported. Lac-hNFs were synthesized by sonication-mediated self-assembly of laccase and copper ions in 5 min at room temperature. About 95% of laccase could be encapsulated in the nanoflowers, and the obtained Lac-hNFs exhibited great enhancement in stability under harsh conditions. The immobilized laccase showed a half-life of 11.7 h at 60 °C, which was about 1.4-fold higher than that of the free enzyme. Meanwhile, Lac-hNFs retained 81% of the initial activity after incubation at 25 °C for 10 days. The laccase in combination with acetosyringone could efficiently decompose tetracycline, doxycycline, and tigecycline. More than 79% of the three TCs were transformed in 1 h. Compared with the free enzyme, Lac-hNFs demonstrated higher capacity in the removal of TCs. Furthermore, Lac-hNFs remained their high degradation capacity after five cycles of reuse. Bacterial growth inhibition test revealed that most of the toxicity of TCs was eliminated after Lac-hNFs treatment. The main transformation products were identified by LC-MS, and the possible degradation pathways were proposed. The interaction mechanism between laccase and TCs was also analyzed using molecular docking. This work provides an efficient way to remove toxic organic pollutants.