In summary, a novel luminescent Zn-MOF 1 with excellent water-stability was fabricated and adequately characterized by a variety of techniques. The structure of 1 features a 2D porous layer network containing the secondary building unit of a double-open hexahedral-like [Zn₈L₈] cage. Adjacent 2D layers are stacked to result in a stable 3D porous architecture via abundant supramolecular interactions. Remarkably, luminescent 1 displays high sensing performance toward Fe³⁺, CrO42−/Cr2O72−, and nitrofuran (NFZ and NFT) and tetracyclines (TCN and OTC) antibiotics in aqueous solution. In fluorescence sensing processes, 1 exhibits excellent fluorescent sensing behavior in the presence of interfering analytes, and good stability and recyclability. The work provides a promising method for multiple detections of ions and organic molecules in aqueous phase.