Because the accurate and rapid detection of antibiotics and pH plays an important role in biological systems and environmental fields, developing suitable and efficient sensors that can simultaneously detect antibiotics and pH has become important. In this work, we successfully designed and synthesized two new one-dimensional coordination polymers based on the mixed ligands L [N,N′-bis(4-methylpyridin-4-yl)-2,6-naphthalene dicarboxylamide] and Hfor CP 1, and M = Ni for CP 2), which were structurally characterized by single-crystal X-ray diffraction, infrared spectroscopy, powder X-ray diffraction, and thermogravimetric analysis. CP 1 and CP 2 can be used as ultraversatile fluorescent sensors, which can sense erythromycin (ERY) and oxacillin (OXC) by turn-on fluorescent enhancement and detect furaltadone (FTD) via the turn-off fluorescent quenching effect, separately. The concentration ranges of different analytes sensed by CPs 1 and 2 were 0−0.046 and 0−0.069 mM for ERY, 0−0.04 and 0−0.028 mM for OXC, and 0−0.155 and 0−0.019 mM for FTD, respectively. Moreover, CP 2 can effectively sense pH, in both a wide pH range and the fine physiological range. The sensors have a rapid luminescence response, good recyclability, and excellent fluorescence stability. More importantly, they not only represent the first example of detecting ERY or OXC based on fluorescent CPs but also are the very rare ultraversatile fluorescent sensors. The fluorescent sensing mechanism for antibiotics and pH was discussed in detail.