Efficient extraction of Ni, Co, Cu, and Mn from low-grade and refractory ores is a common technical challenge. The present study proposes an Acidithiobacillus ferrooxidans-coupled leaching of Ni, Cu, Co, and Mn from oceanic polymetallic nodules and low-grade nickel sulfide ore, and focuses on the electrochemical behavior of the ores in simulated bio-leaching solutions. In the dissolution of polymetallic nodules, A. ferrooxidans facilitates the diffusion of H+ and accelerates electron transfer, producing a decrease in charge transfer resistance and promoting the Mn(IV)-preceding reaction. The use of A. ferrooxidans is beneficial for lower impedance of sulfur-nickel ore, faster diffusion rate of product layer, and better transformation of the Fe3+/Fe2+ couple and S0/S2− couple. A. ferrooxidans increases the potential difference between the nodule cathode and sulfide anode, and increases electron liberation from the sulfide ore. This motivates a significant increase in the average extraction rates of Ni, Co, Cu, and Mn in the bacterial solution. The bio-leaching efficiencies of Ni, Co, Cu, and Mn were as high as 95.4%, 97.8%, 92.2% and 97.3%, respectively, representing improvements of 17.1%, 11.5%, 14.3% and 12.9% relative to that of the germ- and Fe(III)-free acidic 9 K basic system.