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We demonstrate that the thrombin receptor (protease\u2010activated receptor 1, PAR1) exhibits peak expression levels in the spinal cord at term and is a critical regulator of the myelination continuum from initiation to the final levels achieved. Specifically, PAR1 gene deletion resulted in earlier onset of spinal cord myelination, including substantially more Olig2\u2010positive oligodendrocytes, more myelinated axons, and higher proteolipid protein (PLP) levels at birth. <jats:italic>In vitro<\/jats:italic>, the highest levels of PAR1 were observed in oligodendrocyte progenitor cells (OPCs), being reduced with differentiation. In parallel, the expression of PLP and myelin basic protein (MBP), in addition to Olig2, were all significantly higher in cultures of PAR1\u2212\/\u2212 oligodendroglia. Moreover, application of a small molecule inhibitor of PAR1 (SCH79797) to OPCs <jats:italic>in vitro<\/jats:italic> increased PLP and MBP expression. Enhancements in myelination associated with PAR1 genetic deletion were also observed in adulthood as evidenced by higher amounts of MBP and thickened myelin sheaths across large, medium, and small diameter axons. Enriched spinal cord myelination in PAR1\u2212\/\u2212 mice was coupled to increases in extracellular\u2010signal\u2010regulated kinase 1\/2 and AKT signaling developmentally. Nocturnal ambulation and rearing activity were also elevated in PAR1\u2212\/\u2212 mice. These studies identify the thrombin receptor as a powerful extracellular regulatory switch that could be readily targeted to improve myelin production in the face of white matter injury and disease. 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