To investigate the influence of multiple cycles of aging and rejuvenation on the rheological, chemical, and morphological properties of styrene–butadiene–styrene (SBS)-modified asphalt-binders, the asphalt-binders were aged using two laboratory simulation methods, namely a rolling thin film oven (RTFO) test for short-term aging and pressure aging vessel (PAV) for long-term aging. The asphalt-binders were then rejuvenated with three types of rejuvenators (Type I, II, and III) with different dosages (i.e., 6%, 10%, and 14% for the first, second, and third rejuvenation, respectively). A dynamic shear rheometer (DSR) was then used to analyze the effect of rejuvenators on the rheological properties of all the asphalt-binders. The changes in the functional groups and microscopic morphology in the process of multiple aging and rejuvenation cycles were studied using Fourier transform infrared (FTIR) and atomic force microscopy (AFM). The results indicated that the three rejuvenators could soften the stiffness and restore the microstructures of the aged asphalt-binders in the process of repeated aging and rejuvenation from DSR and AFM testing. Considering the rutting and fatigue properties, the Type I rejuvenator exhibited the potential to achieve the desired rejuvenation effects under multiple rejuvenation cycles. During the multiple aging and rejuvenation cycles, the aging resistance of SBSMA decreased gradually from the FTIR results. This inherently limited the number of repeated rejuvenation cycles. This research is conducive to promoting the application of repeated penetrating rejuvenation.