<p>Electrochemical techniques are commonly employed for heavy metal detection. However, due to parasitic capacitance and noise issues arising from their structural design, conventional workstations face limitations in detection performance and system scalability when used for trace analysis in complex environments. To address these limitations, here we developed a custom-designed, low-noise, multi-channel complementary metal-oxide-semiconductor transimpedance amplifier integrated circuit with vertically integrated on-chip electrodes. This system achieves a low noise level of 273.9 fA_RMS and reduces the electrochemical reaction area to just 1 mm², enabling sensitive and specific detection of Cd²⁺ and Pb²⁺ in the wide range of 0.05–500 μg/L. We validated the system’s performance by detecting Cd²⁺ and Pb²⁺ in real seawater samples collected from a depth of 8,448 meters in the Mariana Trench, achieving concentrations of 0.859 μg/L for Cd²⁺ and 0.921 μg/L for Pb²⁺. Compared to inductively coupled plasma-mass spectrometry, our system demonstrated excellent agreement for Cd²⁺ (0.10% deviation) and reasonable consistency for Pb²⁺ (28.0% deviation), reflecting its selectivity for free ions. Our work provides a robust, portable, and miniaturized solution for off-line trace Cd²⁺ and Pb²⁺ detection with seawater background for advanced in situ oceanic monitoring technologies.</p>