Due to the ultra-weak and instantaneous chemiluminescence (CL) of luminol–H2O2 system, developing new catalysts to dramatically enhance and produce persistent CL emission is crucial. In this study, the Cu-metal-organic frameworks (Cu–MOFs) with flower morphology converted from Cu-based metal-organic gels (Cu–MOGs) could catalyze luminol–H2O2 system, exhibiting persistent CL. The possible mechanism of this persistent emission of luminol was attributed to the gradual generation of OH˙, O2˙− and 1O2 in Cu–MOFs–catalyzed luminol–H2O2 system. In addition, OH˙ and O2˙− were continuously recombined into singlet oxygen on the surface of Cu–MOFs which further prolonged the duration time of the CL leading to the persistent emission, due to the longer lifetime of 1O2 compared to OH˙ and O2˙−. Furthermore, based on the high-intensity emission of Cu–MOFs–catalyzed luminol–H2O2 system, the strategy for sensitive response to quercetin was established with good linearity within the range of 0.05–1.2 μM and a detection limit of 49.7 nM. This study provides a new idea for developing persistent CL catalysts. Display omitted •To the best of our knowledge, it is the first example of Cu–MOFs as persistent CL catalysts in luminol–H2O2 system.•The inherent catalytic activity of Cu–MOFs allowed the continuous production of three radicals (OH˙, O2˙− and 1O2).•Recombination mechanism: OH˙ and O2˙− recombined into 1O2 on the surface of Cu–MOFs and further prolonged the CL emission.•The high-intensive Cu–MOFs–luminol–H2O2 CL system was successfully applied to quantify quercetin.