Oligodendrocyte (OL) development undergoes a maturation arrest when premyelinating OL prevalent in preterm fetuses, are exposed to hypoxic injury. Understanding molecular mechanisms controlling OL development may help develop therapeutic strategies in conditions like cerebral palsy. Human fetal neural stem cells (FNSCs) were differentiated into OL and transcriptional changes were analyzed (RNA sequencing). The JAK-STAT cell signaling pathway was implicated in terminal OL maturation. The MO3.13 cell line resembling premyelinating OL was differentiated into mature OL over 7 days, using phorbol 12-myristate 13-acetate (PMA). An increase in the expression of mature-OL marker MBP (qPCR, ICC and flow cytometry) and a decrease in the expression of premyelinating OL markers NG2 and O4 (ICC) validated our findings. Upregulation of the ligand IL-6 and the transcription factor STAT3 using ELISA and qPCR respectively and phosphorylated STAT3 (Western blot), validated the involvement of the JAK-STAT pathway during OL maturation. MO3.13 differentiation was induced using PMA, with and without STAT3 specific inhibitor (Stattic). Flow cytometry demonstrated MBP-positive cells (treated with PMA alone) to be significantly higher than those with both PMA and Stattic, thereby validating our findings. Western blotting also confirmed an increase in phosphorylated STAT3 (pY705) while differentiating MO3.13 with PMA alone whereas no change was observed in pSTAT3 when a STAT3-specific inhibitor was used. These findings underline the association of the JAK-STAT pathway in OL development. This may aid in the development of new therapeutic strategies to overcome the OL maturation arrest and neurological deficits associated with perinatal hypoxic injury.