Prestressed variable depth box-section bridge has been widely used due to its advantages. In recent years, during the period of construction, some accidents occur, and the bottom slab of these bridges has bursting crack. Up to very recently, the research on the damage causes that could be found in the domestic literatures is only with rough analysis but detailed calculation. The primary reasons are made by these notional studies, however secondary reasons are unclear. In practice, the reason should be considered based on the structure instead of construction errors. With a specified engineering sample, 3D FEM analysis is performed so that the distribution of vertical stress on the section of tendon pipeline in the bottom slab is obtained. Result shows that four main external factors have impact on the vertical stress in bottom slab. They are deadweight of the bottom slab, longitudinal pressure, radial force originated from longitudinal bending prestressed tendon, and additional radial force caused by prestressed pipeline deviating from the design. Therefore, parametric analysis with respect to these four factors is conducted as the base for the discussion of the failure mechanism. Results indicate that the primary reason is the additional radial force produced by the radial force of bending tendon cluster and its position deviation from original design. With the longitudinal pressure is applied to, box beam segment of the cracked bottom beam would eventually burst apart due to instability. Based on the failure mechanism, two solutions are recommended for improving the resistant ability in the bursting crack of the bottom slab. They are setting hooked stirrups, and shortening the distance between the spacer bars of prestressed tendon cluster.