The misuse of oxytetracycline (OTC), doxycycline (DOX), tetracycline (TC), and chlortetracycline (CTC) poses a serious threat to human health and it calls for rapid and visual methods. In this study, a novel ratio fluorescent sensor was constructed by simply combining Eu(III) with IRMOF-3. Spectral characterization and DFT theoretical calculations revealed different mechanism of interactions between the MOF-based sensor and different tetracyclines in detail. PCA analysis amplified these differences, enabling the simultaneous identification and differentiation of individual, binary or ternary mixtures of multiple tetracyclines. Subsequently, a rapid fluorescence sensing method (<5 min) for detecting OTC, DOX, TC, and CTC was established with low detection limits of 70, 75, 40, and 168 nM, respectively, which are all below the maximum residue limits by the European Union and the U.S. Food and Drug Administration regulations. A portable visual test strip was also conducted based smartphone with low detection limits of 1 μM, exhibiting an obvious color spectrum transition from blue to purple and finally to pink. Furthermore, the sensor was applied successful to pig feed, milk and veterinary drugs. The results showed good agreement with HPLC-MS/MS analysis.