Bridges are essential for regional traffic and economic development. Once the bridge suffers from a terrorist attack or accidental explosion, it may cause severe losses and impacts on cities and regions. In order to analyze the response and failure of a small box girder bridge under automobile explosion load, explosion simulation tests of the deck and main girder at the bearing part, 1/4 span, and 1/2 span were designed. Then, the explosion conditions of eight standard vehicles are compared. It is found that the damage of the bridge under explosion load is mainly carried out along the longitudinal direction of the bridge, and the change of the explosion point along the longitudinal direction of the bridge significantly impacts the bridge deck breach. When the explosion occurs above the box girder, the response of the box girder is about 1.5-3 times that of the bridge deck. The damage to the superstructure of a prestressed small box girder bridge under a typical vehicle explosion load is localized.