Fluoroquinolone antibiotic (FQ) residues, such as ciprofloxacin (CIP) and ofloxacin (OFLX), have aroused public concerns owing to their serious impact in environmental water or food fields which influence human health. A facile and high-performance sensory method for detecting FQs is highly desirable for practical requirements. Herein, we have presented a luminescent Eu-MOF with unique 2D (4-c) {44.62}-connected topology, which holds the outstanding fluorescent property and excellent chemical stability in aqueous solution for 15 days. Thus, Eu-MOF can be considered as a highly sensitive chemo-sensor for sensing CIP and OFLX with different fluorescent color conversion (red changes to green for OFLX and to blue for CIP) and a low detection limit of 0.693 and 0.802 ppb, respectively. Furthermore, the mechanism of sensing CIP and OFLX was exposed to the photoinduced electron transfer (PET) and dynamic quenching process, as evaluated by DFT calculations and fluorescence lifetime decay measurements. Our work first reports a simple and efficient strategy for recognizing CIP and OFLX with a special luminescence color-change phenomenon based on MOF materials, serving as a meaningful guide for researchers in beneficial applications.