The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor‐kappa B (NF‐κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF‐κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF‐κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF‐κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF‐κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.