Truck suspension is a vital component supporting the weight of the vehicle body and plays an important role in transferring wheel load and isolating external vibration. The uneven load distribution between the middle and rear wheels of a tri-axle heavy truck will directly affect the driving stability and safety of the vehicle. To enhance the truck’s wheel load distribution performance and ride comfort, this paper proposes a new coupling suspension system, including an anti-synchronous middle and rear axle hydraulically interconnected suspension (MR-HIS) and the front axle conventional independent suspension (CIS). Considering the load-bearing characteristics of the middle and rear wheels of the tri-axle heavy truck, a five-degree-of-freedom (5-DOF) half-vehicle model of the truck equipped with MR-HIS is constructed. Further, the dynamics equations of the mechanical-hydraulic coupling system are established according to the impedance transfer matrix method and mechanical-hydraulic boundary conditions, and the truck body motion modes are completely decoupled. The modal analysis demonstrates that compared with CIS the proposed MR-HIS system can reduce the body bounce modal stiffness, increase the modal damping ratio, and enhance the dynamic coupling performance of middle and rear wheels. Subsequently, the frequency response analysis is adopted to evaluate the load distribution and vibration isolation performance of the MR-HIS. The comparison analysis results indicate that the proposed MR-HIS system significantly improves the load balance distribution between the middle and rear wheels and suppresses the load transfer to the front wheel, thus the handling stability of the truck is improved. Meanwhile, the body vibration frequency response analysis shows that the MR-HIS can effectively isolate external vibration and improve driving comfort of the tri-axle heavy truck.