Premature damage to heavy-duty pavement has been found to be significantly caused by the vehicle–highway alignment interaction, especially in mountainous regions. This phenomenon was further verified by field pavement damage investigations and field tests. In order to elucidate the potential mechanism of this interaction, it is important to address the vehicle dynamic loads generated by the interaction between vehicle and pavement. Based on this, the paper realizes a new method of vehicle dynamic load prediction using data mining techniques, namely artificial neural network (ANN) and support vector machine (SVM)). The data, including dynamic loads and highway geometric characteristics, were collected by a wheel force transducer (WFT) and global positioning system (GPS), respectively. The coefficient of determination (R2) and root mean square error (RMSE) were used to evaluate the performance of the prediction models. The results showed that the proposed dynamic load prediction model established by ANN was better than that by SVM. Moreover, the model implied that dynamic loads were highly correlated with curvature and longitudinal grade, and furthermore, curvature was found to have a larger effect. The proposed dynamic load prediction technique provides a feasible and rapid approach to identify pavement damage under complex vehicle–highway alignment interactions.