BACKGROUND AND OBJECTIVE: Accurate finite element (FE) simulation of the optic nerve head (ONH) depends on accurate mechanical properties of the load-bearing tissues. The peripapillary sclera in the ONH exhibits a depth-dependent, anisotropic, heterogeneous collagen fiber distribution. This study proposes a novel cable-in-solid modeling approach that mimics heterogeneous anisotropic collagen fiber distribution, validates the approach against published experimental biaxial tensile tests of scleral patches, and demonstrates its effectiveness in a complex model of the posterior human eye and ONH. METHODS: A computational pipeline was developed that defines control points in the sclera and pia mater, distributes the depth-dependent circumferential, radial, and isotropic cable elements in the sclera and pia in a pattern that mimics collagen fiber orientation, and couples the cable elements and solid matrix using a mesh-free penalty-based cable-in-solid algorithm. A parameter study was performed on a model of a human scleral patch subjected to biaxial deformation, and computational results were matched to published experimental data. The new approach was incorporated into a previously published eye-specific model to test the method; results were then interpreted in relation to the collagen fibers’ (cable elements) role in the resultant ONH deformations, stresses, and strains. RESULTS: Results show that the cable-in-solid approach can mimic the full range of scleral mechanical behavior measured experimentally. Disregarding the collagen fibers/cable elements in the posterior eye model resulted in ~20–60% greater tensile and shear stresses and strains, and ~30% larger posterior deformations in the lamina cribrosa and peripapillary sclera. CONCLUSIONS: The cable-in-solid approach can easily be implemented into commercial FE packages to simulate the heterogeneous and anisotropic mechanical properties of collagenous biological tissues.