The influence of roughness lay directionality on scuffing failure is studied considering different roughness lay direction combinations of the contacting surfaces of a ball-on-disk contact. Using a recently developed scuffing model Li et al., (2013, “A Model to Predict Scuffing Failures of a Ball-On-Disk Contact,” Tribol. Int., 60, pp. 233–245)., the bulk temperature and flash temperature are predicted for each roughness lay combination within the load range from 0.76 GPa to 2.47 GPa in a step-wise manner under the rolling velocity of 10 m/s and slide-to-roll ratio of −0.5 to show substantial impacts of roughness lay directionality on scuffing resistance performance (SRP). It is found (i) the lay direction combination that results into contacts of asperities with small contact radii leads to increased local contact pressures and frictional heat flux, reducing SRP; (ii) the continuous asperity contact along the sliding direction leads to continuous surface temperature rise and lowers SRP; and (iii) the lubricant side leakage caused by the pressure gradient in the direction normal to the sliding direction leads to reduced SRP. With these main mechanisms in effect, the SRP of a contact decreases as the deviation between the roughness texture orientations of the two surfaces increases. The surfaces with their roughness lay directions both perpendicular to the sliding direction exhibits best SRP. The surfaces with one roughness lay direction positioned in line with the direction of sliding and the other positioned perpendicular to the sliding direction shows worst SRP.