S-scheme photocatalytic systems driven by semiconductors are highly promising to degrade deleterious antibiotics in a sustainable manner. Here, ultrathin TiO₂(B) nanosheets-decorated hierarchical In₂S₃ spheres were fabricated for the photocatalytic degradation of tetracycline. The optimized IT-1.5:1 heterojunction attains stronger visible light-harvesting ability, superior electron-hole transfer efficiency, and abundant coupling heterointerfaces to generate reactive radicals, achieving an impressive removal efficiency of 97.3%, which is approximately 3.2 and 2.1-fold greater than TiO₂(B) and In₂S₃. Furthermore, the possible degradation pathways of tetracycline were proposed based on the calculated Fuki indexes and intermediates detected by a HPLC-MS. On In₂S₃/TiO₂(B) interfaces, the migration of electrons from TiO₂(B) to In₂S₃ and an intensive built-in electronic field resulted in S-scheme mode, instead of type-II. The In₂S₃/TiO₂(B) S-scheme structure offers an internal electron channel at the interface and maintains the active sites with high potentials for photocatalysis. This study provides protocols for rational design of S-scheme catalysts for sustainable water purification.