Vast numbers of elongated collagen fibrils are assembled in the extracellular matrix during development then persist unchanged throughout life to maintain tissue shape. How cells distinguish between the synthesis of new fibrils and elongation of existing fibrils cannot be explained with our current understanding of protein secretion. Using CRISPR/Cas9 endogenous engineering of cells to express collagen-I containing photoswitchable and bioluminescent tags, we showed that fibroblasts secrete 100,000 collagen-I molecules/h via the conventional ER-Golgi pathway whereas fibril formation occurs at the plasma membrane at times longer than 24 h and requires functional lysosomes that store procollagen, without degradation, with a t½ of 70 h. We showed that cells from patients with lysosomal storage disorders exhibit impaired collagen fibril assembly. Thus, we have uncovered distinct transport routes for collagen fibril nucleation versus elongation. We suggest targeting lysosomal function could be a new approach for treating collagenopathies for which cures are unavailable.