The skeletal muscle is principally composed of multinucleated myofibers that are surrounded by a layered polymer of extracellular matrix known as basement membrane. It is a tissue of high regeneration potential and the cellular source for repair is the muscle stem cells (MuSCs). MuSCs reside in a precise anatomical niche located between the myofiber's sarcolemma and the overlying basement membrane. Multiple biological mechanisms have been identified to regulate muscle stem cell quiescence, including the inhibition of differentiation, adhesion-dependent anchoring, and translational control, which can be broadly classified into intrinsic or extrinsic pathways. Here, we identify the matrix glycoprotein Fibrillin-1 (Fbn1) as a previously unrecognised, Notch-regulated, cell-autonomous effector, essential for maintaining quiescence in muscle stem cells. Known for its causal role in Marfan syndrome (MFS), a connective tissue disorder that also presents with skeletal muscle atrophy, Fibrillin-1 emerges as a critical niche component that protects stem cells from aberrant growth factor signalling. We demonstrate that targeted deletion of Fbn1 in muscle stem cells leads to dose-dependent quiescence defects, characterised by loss of cellular projections, depletion of the stem cell pool, and decline in long-term muscle function. Mechanistically, loss of Fbn1 upregulates TGF-β signalling, and pharmacological inhibition of this pathway restores quiescence features, stem cell pool, muscle integrity, and performance. These findings reveal a new quiescence-preserving mechanism through ECM-mediated shielding from mitogenic signals, and position stem cell dysfunction as a driver of MFS myopathy.