The main goal of this paper is to explore the mechanism of vortex-induced vibration (VIV) of a streamlined box girder from the perspective of flow field and pressure distribution. In this paper, using the computational fluid dynamic method, the VIV performance of fluid under specific working conditions is simulated and analyzed, especially the distribution and evolution laws of vortex structures in the whole process of VIV are studied in depth. Based on the analysis of the flow field distribution, the corresponding relationship between vortex structures and vortex-induced pressures (VIPs) is discussed. The results demonstrate that the primary cause of VIV for streamlined box girders at large attack angles is the circulation process of the massive vortex structures production and dissipation on the upper surface, rather than the alternate shedding of symmetrical vortex pairs. When vortex structures remain stable, negative VIPs rise in absolute value, negative VIPs occur when vortex structures move backward, and positive VIPs increase when vortex structures fall off.