Recently, metal−organic frameworks (MOFs) have been considered as fluorescence sensors. Herein, we reported the fluorescent TMU-16 for detection of Cu2+ in aqueous solution with high sensitivity and selectivity. Fluorescence quenching was controlled through the cation exchange mechanism between Cu2+ and Zn2+ ions in TMU-16. The strong-fluorescent TMU-16 was converted to a weak-fluorescent TMU-16 (Zn, Cu) and caused highly selective and sensitive detection of Cu2+ in aqueous medium with a 25–400 ppm linear range and 3.96 ppm limit of detection. No interferences from 200 ppm cation solutions of Hg2+, Ag+, Ni2+, Pb2+, Cr3+, Co2+, Cd2+, and Fe3+ were observed for the detection of 25 ppm Cu2+. The possible mechanism for the quenching effect of Cu2+ on the fluorescence sensing of TMU-16 was elucidated by inductively coupled-plasma spectrometry (ICP), X-ray diffraction spectrometry (XRD), Fourier transform-infrared spectrometry (FT-IR), Energy-dispersive X-ray spectroscopy (EDX) and elemental mapping techniques.