<p>Tetracycline is a broad-spectrum antibiotic that can rapidly inhibit bacterial growth, but its excessive usage and improper handling can lead to its discharge into water, soil, and other ecosystems, posing a significant hazard to ecology and human health. Photocatalysis is considered the most attractive solution for addressing this problem. However, most photocatalysts suffer from nanoparticle agglomeration, high electron-hole recombination rates, and low degradation efficiency. Herein, we offer a straightforward <i>in situ</i> hydrothermal phase separation strategy for synthesizing ZnIn₂S₄ particles on cellulose/chitosan composite sponges for the effective adsorption and degradation of tetracycline in wastewater. The prepared ZnIn₂S₄ composite sponge displayed a remarkably porous structure (with pore diameters of 150–500 µm), uniformly distributed ZnIn₂S₄ nanoparticles (with diameters of approximately 15 nm), a narrow bandgap (2.88 eV), and exceptional compressibility. Owing to these characteristics and the affinity sites of the polysaccharide sponge skeleton, ZnIn₂S₄ composite sponges represent an innovative model of synergistic adsorption-photocatalytic degradation. The prepared ZnIn₂S₄ composite sponge had a removal efficiency of up to 91.5% for tetracycline under sunlight irradiation and remained effective after eight consecutive cycles. This study highlights the potential application prospects of ZnIn₂S₄ composite sponges in the sustainable and environmentally friendly treatment of antibiotics.</p>