<p>Defending behavior of bystanders effectively reduces school bullying. Perceived social support and empathy have been demonstrated to facilitate adolescents’ defending behavior. Understanding whether perceived social support affects defending behavior via empathy is vital for elucidating the underlying psychological mechanisms. However, previous studies only focused on the between-person level, leaving the dynamic, within-person processes underlying their interplay over time unclear. Furthermore, no study has integrated these elements into a unified model to explore the mediating roles of the two dimensions of empathy and the moderating role of childhood maltreatment. The current study followed 2,407 Chinese adolescents (50.23% girls, <i>M</i>_age = 12.75, <i>SD</i> = 0.58 at baseline) from seven schools at three time points with a one-year intervals. The result of the parallel process latent growth curve model indicated the pairwise co-development process among perceived social support, empathy, and defending behavior. The result of the random intercept cross-lagged model indicated significant associations among perceived social support, empathy, and defending behavior at the between-person level. At the within-person level, virtuous circles existed in the relation between defending behavior and perceived social support as well as the relation between perceived social support and empathy. Affective empathy consistently predicted subsequent defending behavior over time and mediated the longitudinal relation between perceived social support and defending behavior. The moderating role of childhood maltreatment was observed in the longitudinal associations. By adopting a developmental perspective, the current study identifies the dynamic interplay among perceived social support, empathy, and defending behavior, providing specific targets for school bullying interventions.</p>