Herein, a novel MXene aerogel-CuO/carbon cloth (MXA-CuO/CC) electrochemical sensor was constructed, and the synergistic adsorption of heavy metal ions by oxygen vacancies and Bi (III) was investigated with Cd2+ and Pb2+ as detection targets. The oxygen vacancies of CuO have a strong affinity for heavy metal ions, which promoted the adsorption of Cd2+ and Pb2+ on the electrode surface. In addition, the introduced Bi (III) can form alloys with heavy metal ions, which effectively enhanced the adsorption capacity of sensing electrodes for Cd2+ and Pb2+. Differential pulse anodic stripping voltammetry (DPASV) was used to study the performance of MXA-CuO/CC sensitive electrode for the detection of Cd2+ and Pb2+ separately and simultaneously. The constructed sensing electrode has excellent detection performance, and can detect Cd2+ (4 μg L−1– 800 μg L−1) and Pb2+ (4 μg L−1– 1200 μg L−1) simultaneously with detection limits of 0.3 μg L−1 (Cd2+) and 0.2 μg L−1 (Pb2+), respectively. The proposed sensor electrode also has good anti-interference performance, excellent stability and reproducibility. It is worth mentioning that the proposed method can accurately detect Cd2+ and Pb2+ in food and water samples, which is consistent with the detection results of inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectroscopy (AAS).