Effective removal of antibiotics from aqueous solutions has emerged as a hot research topic in wastewater treatment. Photocatalytic degradation of antibiotics is one of the most effective methods to reduce ecological damage and environmental pollution. In this work, a novel photocatalyst consisting of Z-type heterojunction Bi2S3/Bi4Ti3O12 (BS/BTO) with visible light responses was prepared by an in situ growth method, and the obtained material was used for the degradation of tetracycline hydrochloride (TC). The best performing photocatalyst was BS/BTO-2, which exhibited high photocatalytic activity. The rates of TC degradation reached 97.9% within 40 min of illumination. The photocatalyst demonstrated a high stability and reproducibility even after 5 cycles. Electron spin resonance (EPR) tests and quenching experiments established that ·O2- and h+ were the main species responsible for the elimination of TC. On the basis of theoretical calculations and experimental data, a possible mechanism for the photocatalytic degradation of TC has been proposed. The heterojunction structure, which effectively increases the visible light absorption range and decreases the compounding efficiency of photogenerated electrons and holes, is principally responsible for the photocatalytic performance of BS/BTO. Additionally, liquid chromatography-mass spectrometry (LC-MS) was utilized to investigate the formation and degradation of reaction intermediates. The nontoxicity of the solution after tetracycline degradation was verified by cultivating wheat seeds. This work offers guidance for bismuth-based photocatalysts in the field of sustainable wastewater treatments.