In this work, a novel core-shell structured CuO@TAPB-DMTP-COF composites were synthesized by encapsulating CuO nanorods into TAPB-DMTP-COF host matrix. The structural properties of the composites were revealed by X-ray diffraction pattern (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Scanning electron microscope (SEM), and Transmission electron microscopy (TEM). Subsequently, the CuO@TAPB-DMTP-COF composites were immobilized on the glass carbon electrode (GCE) surface to fabricate an electrochemical sensor for dopamine detection. CuO functions as a highly catalytic active substance to accelerate the charge transfer rate of the reaction, while TAPB-DMTP-COF with a large electroactive surface area enhances the adsorption ability of the modified electrode toward the target molecules. The main parameters during the analytical procedure were investigated in detail, and the analytical performance was improved significantly due to the synergistic effects of CuO and TAPB-DMTP-COF. Under the optimal conditions, the dopamine peak responses are linear in a wide range from 0.07 to 800 μM, and the detection limit is as low as 0.023 μM. Furthermore, the dopamine sensor also exhibits good repeatability, stability, and accurate detection ability in actual samples. This study will expand the application of organic porous material based composites in ultra-sensitive electrochemical bioanalysis.