Following CNS injury, reactive astrocytes and extracellular matrix (ECM) contribute to glial scar formation, but the mechanisms regulating scar ECM remain unclear. Because type I collagen, a proline-rich ECM protein composed of COL1A1 and COL1A2, is enriched in glial scars and can be produced by astrocytes, we hypothesized that astrocytic EPRS1 promotes collagen synthesis and scar formation. Transcriptomic analyses of TBI, stroke, and GBM showed shared collagen-rich ECM remodeling with increased COL1A1/2, along with high estimated proline demand in TBI and elevated EPRS1 expression in TBI and H₂O₂-treated primary astrocytes. Scratch injury and hippocampal stab injury (HSI) increased GFAP and COL1A1. In focal GiD mice, selective astrocyte reactivity without mechanical injury was sufficient to induce COL1A1 accumulation and glial scar formation. After HSI, pharmacological EPRS1 inhibition with DWN12088 reduced GFAP and COL1A1 and improved object recognition and location memory. Astrocyte-specific EPRS1 knockdown similarly attenuated GFAP, COL1A1, glial scar formation, and cognitive impairment. These findings suggest that astrocytic EPRS1-dependent collagen synthesis contributes to glial scar formation and cognitive dysfunction after CNS injury, identifying EPRS1 as a potential therapeutic target.