The fatigue life of orthotropic steel decks (OSDs) is significantly affected by vehicle loads, and the local stress response of OSDs is sensitive to the transverse position of vehicle loads. However, the presence of autonomous vehicles is likely to change the transverse distribution of vehicles within the lane, thereby affecting vehicle-induced fatigue damage to OSDs. Therefore, it is necessary to evaluate the potential effect of autonomous vehicles on the fatigue life of OSDs so that appropriate strategies can be implemented to control the transverse positions of autonomous vehicles passing the bridge deck. To this end, fatigue damages of several typical fatigue details in a conventional OSD (COSD) and a lightweight composite OSD (LWCD) induced by vehicle loads were calculated based on finite element analysis, and their fatigue lives were evaluated based on Miner’s Rule, in which different transverse distribution patterns of autonomous vehicles and their proportions in the mixed traffic flow were considered. The results indicate that fatigue lives of both the COSD and the LWCD can be negatively affected by autonomous vehicles traveling across the bridge without any constraints on the transverse distribution, especially when their proportion in the mixed traffic flow exceeds 30%. Compared to the scenario without autonomous vehicles, the fatigue damage of most fatigue details in OSDs may increase by 51% to 210% in the most unfavorable case due to the presence of autonomous vehicles. Nevertheless, it is feasible to extend the fatigue life of OSDs by optimizing the transverse distribution of autonomous vehicles. Specifically, the fatigue life of most fatigue details in the COSD could be extended by more than 86% in the most favorable case when a bimodal Gaussian distribution is adopted as the transverse distribution pattern of autonomous vehicles. Moreover, both the negative and positive effects of autonomous vehicles on the fatigue life of the COSD are more significant than those of the LWCD in most cases. The results can provide references for the maintenance of OSDs under the action of autonomous vehicles.