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Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF-MAP2K signaling plays a key role in axon elongation during nervous system development. Here, we show that conditional expression of a constitutively kinase-activated BRAF in mature corticospinal neurons elicited the expression of a set of transcription factors previously implicated in the regeneration of zebrafish retinal ganglion cell axons and promoted regeneration and sprouting of corticospinal tract (CST) axons after spinal cord injury in mice. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, resulting in improved recovery of motor function. Noninvasive suprathreshold high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) activated the BRAF canonical downstream effectors MAP2K1/2 and modulated the expression of a set of regeneration-related transcription factors in a pattern consistent with that induced by BRAF activation. HF-rTMS enabled CST axon regeneration and sprouting, which was abolished in MAP2K1/2 conditional null mice. These data collectively demonstrate a central role of MAP2K signaling in augmenting the growth capacity of mature corticospinal neurons and suggest that HF-rTMS might have potential for treating spinal cord injury by modulating MAP2K signaling. Stimulating growth: Recovery from spinal cord injury is hindered by the inability of CNS neurons to regenerate severed axons, and there are no effective approaches to promote axonal growth after a CNS injury. Here, Boato et al. showed that conditional BRAF activation using genetic approaches activated MAP2K signaling and promoted axonal regeneration after spinal cord injury in mice. Similarly, non-invasive repetitive transcranial magnetic stimulation (rTMS) activated MAP2K signaling and enhanced axonal regeneration and functional recovery, suggesting that rTMS might be a valuable treatment option for spinal cord injury. —MM [ABSTRACT FROM AUTHOR]