With ongoing technological improvements and research in the field of autonomous vehicles, it is becoming evident that the technology has the potential to substantially affect the transportation sector. Although the potential benefits with respect to productivity increases, cost decreases, and safety are evident, the potential for these vehicles to negatively or positively affect the transportation infrastructure is unclear. In this study, the influence of truck loadings positioning on the long-term performance of transportation infrastructure was estimated by carrying out performance simulations of pavement structures. Scenarios considering both full and partial use by autonomous trucks were considered. In all cases, performance was estimated with respect to rutting, fatigue cracking, and overall pavement smoothness, and the results were compiled in terms of reduced pavement thickness. It was found that if controlled appropriately, autonomous trucks could be highly beneficial for the pavement infrastructure design, and they would be most effective when they represented more than 50% of the total truck traffic. It was also found that in the absence of appropriate control, specifically by repeatedly positioning trucks in the same location, the amount of damage could be highly detrimental, and noticeable influences may occur at autonomous truck volumes as low as 10%.