Objectives Parallel with body growth and development, bone structure in non‐adults is reorganized to achieve the particular design observed in mature individuals. We traced the changes in three‐dimensional trabecular microarchitectural design during the phases of locomotor maturation to clarify how human bone adapts to mechanical demands. Materials and Methods Micro‐CT was performed on biomechanically‐relevant subregions of the proximal femur (medial, intermediate and lateral neck regions, intertrochanteric region, metaphyseal region) from early postnatal period to late childhood. Results Developmental patterns of trabecular microarchitecture showed that gestationally overproduced bone present at birth underwent the most dramatic reduction during the first year, followed by a reversing trend in some of the quantitative parameters (e.g., bone volume fraction, trabecular anisotropy). Certain regional anisotropy already present at birth is further accentuated into the childhood suggesting an adaptation to differential loading environments. Trabecular eccentricity in the femoral neck was particularly accentuated during childhood, giving the medial neck—the site mostly loaded in walking—superior microarchitectural design (high bone volume fraction and anisotropy, the earliest appearance and predominance of plate‐ and honeycomb‐shaped trabeculae). Discussion While providing quantitative data on how bone microarchitecture adapts to increasing mechanical demands occurring during the phases of locomotor maturation, the study reveals how regional anisotropy develops in the proximal femur to ensure a functional and competent bone structure. Decomposing the region‐specific patterns of bone mass accrual is important in understanding skeletal adaptations to bipedalism, as well for understanding why fractures often occur location‐dependent, both in pediatric and elderly individuals.