<p>Aging of asphalt binders plays a critical role in governing the fatigue performance of asphalt mixtures and pavements. Compared to traditional pressure aging vessel (PAV), the recently developed accelerated laboratory thermal aging approach has been shown to more closely replicate the aging mechanisms occurring in the field. This study aimed to investigate the influence of accelerated laboratory thermal aging on the fatigue resistance of base binder and styrene–butadiene–styrene–modified binders with varying polymer contents and molecular structures. All binders were subjected to both accelerated laboratory thermal aging and PAV aging, and then the fatigue behavior was characterized using time sweep (TS) and linear amplitude sweep (LAS) tests. The results indicate that the fatigue life of base binder obtained from the TS test increased with aging time, whereas a two-stage decline was observed in the LAS-based fatigue results. The equivalent accelerated laboratory thermal aging duration corresponding to PAV aging was found to be strongly dependent on polymer content, polymer architecture, and the fatigue evaluation method because of the large differences in aging temperature and pressure. Additionally, the influence of polymer content and structure on fatigue life gradually diminished with prolonged laboratory thermal aging time due to polymer degradation.</p>