The pavement responses obtained from the validated finite element modeling of new-generation wide-base tires (NG-WBTs) and a conventional dual-tire assembly (DTA) are presented. Features of the adopted finite element model, such as three-dimensional contact forces, dynamic analysis, and nonlinear anisotropic base materials, are not considered in the conventional analysis of flexible pavements. Furthermore, the input for the model was intended to simulate a large range of scenarios for the national pavement system. The NG-WBT showed consistently higher pavement responses than the DTA, and the difference decreased as pavement thickness increased. (Pavement thickness varied from 225 to 1,012.5 mm.) The average percentage difference of the longitudinal tensile strain at the bottom of the asphalt concrete layer was 14.7% and 23.2% for thick and thin pavements, respectively. In a few cases of vertical shear strain in the subgrade for thin pavement, the response was higher for the DTA than for the NG-WBT. For the same responses in thick pavement, the average percentage difference was 4.4%. If critical pavement strains are used as inputs into transfer functions, which estimate pavement life, results of this study could serve as indicators of increased potential damage when NG-WBTs are used. However, market penetration of the NG-WBT and its use within the truck axle configuration need to be taken into consideration. Additionally, environmental and economic benefits of using NG-WBTs may offset the potential increase in pavement costs.