To reduce the computing work and improve the efficiency of vehicle-bridge coupling analysis when using traditional fully coupled method, a high efficiency highway vehicle-bridge interaction analysis system was established based on improved binary search and isoparametric mapping. The finite element model of the bridge was simulated using ANSYS, the multiple refined dynamic vehicles were modeled in MATLAB, and the inter-history iteration method was used to analyze the bridge subsystem and vehicle subsystem separately. The quadrilateral isoparametric mapping and improved binary search method were introduced for quick determination of interpolation coefficient and loading position of vehicle-bridge contact point to realize the quick automatic loading of wheel load. Based on the spring-mass model passing through a simply supported beam and a running test of a long-span suspension bridge, the proposed analysis system was compared with the classical numerical analysis method, measured data and traditional time step iteration method. The results show that the proposed analysis system exhibits a good computing efficiency and accuracy and rapid convergence, which can provide a reference for the bridge spatial response analysis under large and highly random traffic flow.