Antibiotics, widely used in the fields of medicine, animal husbandry, aquaculture, and agriculture, are ubiquitously present in water systems, posing a serious threat to the ecological environment and human health. It is essential to develop a fast, sensitive and straightforward analytical method for sensing antibiotics in aqueous solution. In this work, a 3D luminescent metal-organic framework (MOF), named Cd-BTDI, has been synthesized, featuring high structural stability in water. The intense green luminescence with an emission peak at 509 nm is quite stable in aqueous and common organic solvents, providing a good foundation to fabricate a potential chemical sensor. Cd-BTDI exhibits selective and sensitive detection performance for tetracycline (TC) and oxytetracycline (OTC) antibiotics, with fast response and good anti-interference. The limits of detection (LODs) for TC and OTC are 0.071 μΜ and 0.062 μΜ, respectively. By introducing the commercially available polymer polymethyl methacrylate, a reusable sensing film can be fabricated for on-site visual detection of trace tetracycline antibiotics. In addition, Cd-BTDI can detect tetracycline antibiotics in three kinds of typical real water matrices (tap, lake and river water), showing a great potential for practical uses.