• Three fluorescence-enhanced rare-earth ions labeled porous silica nanoprobes were developed. • Multicolor fluorescence responses allow for sensitive and selective detection of antibiotics. • Digital mapping of fluorescence array enables rapid identification of multiple antibiotics. • Applicability of method was demonstrated for detecting multiple residues in milk. The misuse of antibiotics not only has adverse effects on the environment but also has become a serious problem that threatens human health. However, the simultaneous, rapid, and accurate detection of various antibiotic residues remains a challenge for actual samples. Herein, a new sensing strategy was developed by using fluorescence-enhanced rare-earth ion-labeled mesoporous silica nanoprobes (MSN–COOH–Eu 3+ , MSN–COOH–Tb 3+ , and MSN–COOH–La 3+ ) and their array to detect three representative antibiotics, namely, oxytetracycline (OTC), norfloxacin (NFX), and gatifloxacin (GTFX). The three rare-earth ion-labeled nanoprobes exhibited red, green, and blue fluorescence when reacting with OTC, NFX, and GTFX, respectively, because of the antenna effect of rare-earth ions or restricted conformational rotation of antibiotics. The multicolor digital imaging pattern generated from the three-nanoprobe array also enables the rapid identification of OTC, NFX, and GTFX in various combinations. Meanwhile, the linear detection ranges for OTC, NFX, and GTA were 11–30, 0–0.9, and 0–1.4 μM, respectively, and their detection limits were 0.016, 0.007, and 0.005 μM, respectively. Furthermore, satisfactory recoveries of 90.1%–107.8% were obtained in OTC, NFX, or GTFX-spiked raw milk, indicating the potential application of our method for monitoring various antibiotic residues in daily food safety controls.