Hypertension, a disease with known sexual dimorphism, accelerates aging associated arterial stiffening. In this study, we tested the effect of biological sex and the role of the matrix remodeling enzyme lysyl oxidase like 2 (LOXL2) in hypertension induced arterial stiffening. Hypertension was induced by Angiotensin II (AngII) infusion. Blood pressure and pulse wave velocity (PWV) were measured noninvasively. Wire myography and uniaxial tensile testing were used to test aortic vasoreactivity and mechanical properties. Aortic wall composition was examined by histology and Western blotting. Uniaxial stretch of cultured cells was used to evaluate the effect of biomechanical strain. LOXL2's catalytic function was examined using knockout and inhibition. Ang II infusion induced hypertension in both genotypes and sexes. Hypertensive WT males had higher PWV and passive stiffness. Aortic remodeling with increased wall thickness, intralamellar distance, higher LOXL2, collagen I, and collagen IV content was noted in WT males. Females did not exhibit increased PWV. LOXL2-depletion improved aortic mechanics in both sexes. LOXL2-depletion improved hyper-contractility in males but not females. Hypertensive cyclic strain contributed to LOXL2 upregulation in the cell-derived matrix in VSMCs. LOXL2's catalytic function facilitated VSMC alignment in response to biomechanical strain. In males, arterial stiffening in hypertension is driven by VSMC response and matrix remodeling; females are protected from stiffening independent of LOXL2. VSMCs are the primary source of LOXL2 in the aorta. Hypertension increases LOXL2 processing and collagen I accumulation in the aorta. Overall, LOXL2 depletion offers protection in young hypertensive males and females.