To deepen the understanding of the collapse of simply-supported highway bridges, the shear force distribution-based and stability theory-based analysis methods for bridge collapse were proposed. The finite element approach (FEA) was adopted and validated against the explosion test on RC piers through comparisons with experimental reflected overpressure-time histories and the pier damage patterns. Then, based on the validated FEA, the FE model of a prototype highway bridge was established, and explosion sources were determined as the sedan bomb specified by Federal Emergency Management Agency (FEMA). By varying the standoff distances, the explosion analyses were carried out, and the collapse response of the prototype highway bridge was examined from the both shear force distribution and stability theory perspectives. Finally, a safe standoff distance for the prototype bridge under sedan bomb explosion was determined. This work can improve the understanding of bridge collapse, and help city planners properly set standoff barriers.