The effect of wheel configuration on critical airfield pavement responses during takeoff was calculated, and variables, usually omitted in conventional pavement analysis, were considered. The numerical analysis matrix consisted of two takeoff speeds, two inflation pressures, two pavement structures, and four wheel configurations. One of the pavement structures was built at the National Airport Pavement Test Facility and had been previously described in the literature. The method used in this study advanced current knowledge in two respects. First, the study examined not only the tensile strains at the bottom of the asphalt concrete (AC) layer (fatigue cracking) and vertical strain on top of the subgrade (rutting) but also the transverse surface strain (surface cracking) and vertical shear strains (near-surface cracking and rutting). Second, several assumptions about existing methods were advanced. These assumptions included (a) nonuniform three-dimensional contact stresses instead of uniform one-dimensional vertical stresses over a circular contact area, (b) viscoelastic and nonlinear material characterization for AC and granular material under high stress levels in lieu of a linear elastic model, and (c) load variation with time to reflect takeoff. Transverse surface strain and vertical shear strain in the subgrade were most affected by wheel configuration. In addition, the variables had varying influence on pavement responses and wheel interaction. For instance, takeoff speed affected vertical strain on top of the subgrade but did not affect transverse surface strain. Tire inflation pressure modified wheel interaction for shear strain in the AC but not in the subgrade.