This study investigates the association between handedness and brain functional connectivity patterns in 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. The results show that left-handers exhibit increased global functional connectivity density in the left-hand motor area and decreased connectivity in the right-hand motor area compared to right-handers. A connectivity-based index of handedness effectively differentiates between right- and left-handers. The laterality of hand-motor connectivity varies across unimodal sensorimotor cortices, heteromodal areas, and the cerebellum, and these differences are consistent across all regions of interest in both the Discovery and Replication subsamples. The findings suggest that handedness is associated with distinct neural organizations in left-handers and right-handers, with left-handers showing higher connectivity within the right hemisphere and right-handers within the left hemisphere. These results highlight the importance of functional connectivity in understanding hand motor behaviors and provide a neurobiological index of handedness that correlates with children's handedness scores.This study investigates the association between handedness and brain functional connectivity patterns in 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. The results show that left-handers exhibit increased global functional connectivity density in the left-hand motor area and decreased connectivity in the right-hand motor area compared to right-handers. A connectivity-based index of handedness effectively differentiates between right- and left-handers. The laterality of hand-motor connectivity varies across unimodal sensorimotor cortices, heteromodal areas, and the cerebellum, and these differences are consistent across all regions of interest in both the Discovery and Replication subsamples. The findings suggest that handedness is associated with distinct neural organizations in left-handers and right-handers, with left-handers showing higher connectivity within the right hemisphere and right-handers within the left hemisphere. These results highlight the importance of functional connectivity in understanding hand motor behaviors and provide a neurobiological index of handedness that correlates with children's handedness scores.