Xenopus laevis tadpoles can regenerate the spinal cord after injury but this capability is lost during metamorphosis. Comparative studies between pre-metamorphic and metamorphic Xenopus stages can aid towards understanding the molecular mechanisms of spinal cord regeneration. Analysis of a previous transcriptome-wide study suggests that, in response to injury, the JAK-STAT pathway is differentially activated in regenerative and non-regenerative stages. We characterized the activation of the JAK-STAT pathway and found that regenerative tadpoles have an early and transient activation. In contrast, the non-regenerative stages have a delayed and sustained activation of the pathway. We found that STAT3 is activated in response to injury mainly in Sox2/3+ ependymal cells, motoneurons and sensory neurons. Finally, to study the role of temporal activation we generated a transgenic line to express a constitutively active version of STAT3. The sustained activation of the JAK-STAT pathway in regenerative tadpoles reduced the expression of pro-neurogenic genes normally upregulated in response to spinal cord injury, suggesting that activation of the JAK-STAT pathway modulates the fate of neural progenitors.