The human dura mater is known to impact vastly traumatic brain injury mechanopathology. In spite of this involvement, dura mater is typically neglected in computational and physical human head models. The lack of location-dependent microstructural and related mechanical data of dura mater may be considered a rationale behind this simplification. The anisotropic nature of dura mater under various loading conditions so far remains unelucidated. Furthermore, principal collagen fiber orientation is yet to be quantified for a morpho-mechanically-informed material model on the dura mater. This study aims to assess how location-dependent mechanical anisotropy is linked to principal collagen fiber orientation. Uniaxial extension tests were performed in a heated tissue bath for 60 samples from six individuals and correlated to the three-dimensional collagen structure in four individuals using second-harmonic generation (SHG) imaging. Failure stress and stretch at failure, elastic modulus, and a microstructurally motivated material model were integrated to examine local differences in dura mater morpho-mechanics. The quantitative observation of collagen fiber orientation and dispersion confirmed that collagen is highly aligned in the human dura mater and that both fiber orientation and dispersion differ depending on the location investigated. This observation provides a possible explanation for the previously observed isotropic mechanical behavior, as the main collagen fiber direction is not oriented along the anterior-posterior or medial-lateral direction at most of the mapped locations. Additionally, these site-dependent structural properties have implications for the mechanical load response and therefore potentially for the regional functions dura mater has to fulfill. The here chosen non-symmetrical fiber dispersion material model fits the data well and provides a comprehensive parameter base for further studies and future finite element models. STATEMENT OF SIGNIFICANCE: The human dura mater greatly affects traumatic brain injury mechanisms, but it is often ignored in computational and physical head models. This is because there is a lack of detailed microstructural and mechanical data specific to the dura mater. Its anisotropic nature and collagen fiber orientation have not been fully understood, hindering the development of an accurate material model. Hence, this study combines morphological data on collagen fiber orientation and dispersion at multiple locations of human cranial dura mater, and links microstructure to location-specific load-displacement behavior. It provides microstructurally informed mechanical information towards realistic head models for predicting location-dependent tissue behavior and failure for assessing brain injury and graft material development.