In order to investigate the interaction effect between the transient wear behavior and the lubrication characteristics of the main bearing in low-speed diesel engine under the actual working condition, a coupling model of mixed elastohydrodynamic transient lubrication and time-varying wear is constructed. The transient lubrication model considering the journal misalignment and elastic-plastic asperity contact is used to consider the lubrication characteristics of the main bearing. The wear mechanism of the main bearing material (Babbitt alloy) is found to be surface fatigue wear mainly by the experiments under the equivalent lubrication state, thus the wear model is based on the fatigue damage theory. Several experiments were conducted to verify the accuracy of the coupled model. It is found that the wear gradually increases with increases with wear time, and meanwhile, the lubrication characteristics also change with the wear status. In addition, the effect of the parameters including radius clearance, rotation speed, journal misalignment and bearing loads on the properties of lubrication and wear were investigated. This work would provide practical support for the investigation of wear and lubrication behavior under actual low-speed diesel engine operation.