The main cable bent around the saddle of the suspension bridge is subjected to the wind, the vehicle, the bridge’s own weight and the corrosive media. The coupling of the three loads and the environments causes the friction, the corrosion, and the fatigue (tribo-corrosion-fatigue) among the wires inside the main cable. In this paper, a wire bending tribo-corrosion-fatigue test rig was designed and developed. The effect of fatigue load on the bending friction behaviors between the cable wires in ultrapure water and 3.5% NaCl solution was explored. The tribological properties and electrochemical corrosion behaviors under different fatigue loading ranges were investigated. The tribo-corrosion-fatigue interaction between the cable wires was quantitatively characterized, and the mechanism of the interaction was analyzed. The results demonstrate that the increasing fatigue load exacerbates the coupling damage of the cable wires attributed to the enhanced interaction. The findings carry theoretical importance when assessing the main cable’s deterioration and the load-bearing safety of a suspension bridge.