A need exists to determine the fatigue life of multi-span continuous bridges in the design stage. It is difficult to conduct a full-scale fatigue test of a bridge, hence the simulation of bridge-vehicle interaction dynamics is important to estimate the fatigue life of bridges. The vehicles entering the bridge are random in nature. In the present study, the arrival time of the vehicles is considered a random variable following Poisson process to simulate the actual traffic. The bridge-vehicle coupled system equations have been derived wherein the vehicle arrival rate appears as random variable casting difficulty in obtaining a direct solution. The solution approach has been devised using Orthogonal Polynomial Expansion method. Response statistics so obtained for a multi-span continuous bridge has been used in fatigue life estimation involving crack initiation phase and crack propagation phase modifying conventional linear damage rule. The sequence of loading is also considered in the modified fatigue formulation. The effect of the vehicle speed, road surface irregularity and the arrival rate of the vehicle on fatigue life estimation of the bridge have been studied.