An electrochemical sensor based on a NH2-MIL-53(Al)/polypyrrole (PPy) nanocomposite modified gold electrode for determination of ultra-trace Pb (II) and Cu (II) was developed. The PPy nanowires were synthesized through a chemical polymerization process, and the NH2-MIL-53(Al) was deposited on the PPy nanosubstrates by an in-situ electrochemical method. Field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) spectroscopy and attenuated total reflection infrared (ATR-IR) spectroscopy were used to study the structural features of the nanocomposite. The electrochemical behavior of the NH2-MIL-53(Al)/PPy nanocomposite toward Pb (II) and Cu (II) was investigated by differential pulse voltammetry (DPV) technique. Due to the synergistic effect of the PPy and NH2-MIL-53(Al), the nanocomposite modified electrode exhibited good sensing performance to Pb (II) and Cu (II) in the range of 1–400 μg L−1 with detection limit of 0.315 μg L−1 and 0.244 μg L−1, respectively. The limit of detection and the sensitivity of the NH2-MIL-53(Al)/PPy nanocomposite modified electrode were significantly enhanced than those of the individual modified electrodes. The effective electrochemical property of the nanomaterial for the Pb (II) and Cu (II) could provide a new direction for the heavy metal ions determination.