Defect‐enriched mesoporous CuO nanosheets (NSs) were constructed to investigate the cooperative photo‐Fenton and photothermal‐Fenton catalysis on degradation of fluoroquinolones (FQ) antibiotics. The oxygen vacancies provide abundant active sites to bind the substrates and inhibit charge recombination, by all means to enhance Fenton‐like activity. Two disparate spectral selective functions of photoexcitation and photothermal conversion were achieved on CuO NS, which to promote the Fenton activity synergistically. Visible light induced photoexcitation to facilitate the generation of Cu+ and •OH, while near‐infrared light converted into heat to promote charge separation and accelerate medium transport. Ultimately, as a unitary catalyst system, the CuO NS integrated the Lewis acid catalysis, Fenton‐like catalysis and photothermal catalysis that rapidly and sustainably degraded antibiotics under near‐neutral conditions.