Previous studies indicate region-specific age- and sex-related changes in cerebral microvasculature. Using whole-brain vascular architecture mapping (VAM), our objective was to map and assess these changes in human microvasculature . Cardiovascular healthy women (n = 40) and men (n = 32) with unifocal low-grade glioma, matched for age [range: 20-70 years] and BMI, were examined on the non-tumor hemisphere with a combined spin and gradient echo echo-planar imaging sequence at 3 T MRI. Vessel vortex curves were obtained by pair-wise plotting changes in relaxation rates R2* and R2 during contrast agent bolus passage, which each generate a set of VAM parameters that characterize microvascular properties, such as vessel type, lumen size, or blood flow. Averaged VAM values of cortical grey matter, white matter, putamen, globus pallidus, caudate nucleus, thalamus, insular cortex, and hippocampus were assessed for age- and sex-related changes. With age, dominant vessel types changed from capillaries to an arteriole-dominated profile, particularly in insula, thalamus, and globus pallidus. In white matter, blood flow velocity decreased significantly with aging for both sexes (r = -0.33, p = 0.004). In women, aging was associated with an increase in microvessel caliber, particularly in thalamus (r = 0.39, p = 0.01) and insula (r = 0.34, p = 0.03). In all grey matter areas, women had a higher microvessel density than men (4.33 ± 0.26ˑ10 ms vs. 4.18 ± 0.26ˑ10 ms; p = 0.025, respectively). Aging affects microvasculature differently across brain regions in women and men, especially in thalamus and insula.