An optimized lubrication condition of the crosshead bearing in low-speed marine diesel engines is pivotal to its prolonged service life, because the bearing oscillates at a low speed and the direction of the high load is always downward. Theoretical studies on the tribology of the crosshead bearing are very limited, with existing studies ignoring the effects of connecting rod inertia. Herein, a new multi-body tribo-dynamic model for the engine is presented by coupling the dynamics models of the connecting rod, piston assembly, and crosshead assembly with the mixed lubrication models of the multiple lubricated joints including the crosshead bearing. Based on this new multi-body tribo-dynamic model, the bearing load, journal center trajectories, friction torque, and minimum oil film thickness were calculated and compared with those based on the simplified method used in the previous literatures. The results show that due to the connecting rod inertia, the bearing load in the transverse direction calculated by the simplified algorithm is different from that calculated by the tribo-dynamic model proposed in this study. Compared with the results based on the previous simplified method, the inertia of the connecting rod reduces the friction torque of the bearing, especially at the end of the upward stroke.