This study investigates the relationship between handedness and brain functional connectivity patterns in 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. It finds that left-handers have increased global functional connectivity density (gFCD) in the left-hand motor area and decreased it in the right-hand motor area compared to right-handers. A connectivity-based index of handedness effectively differentiates right- and left-handers. The laterality of hand-motor connectivity varies across unimodal sensorimotor cortices, heteromodal areas, and the cerebellum, and is consistent across all regions of interest in the Discovery and Replication subsamples. The study shows a strong association between handedness and the laterality of functional connectivity patterns without differences in structural connectivity, brain morphometrics, or cortical myelin between left, right, and mixed-handed children. Handedness, the preference for using one hand over the other, is a trait associated with complex brain asymmetries influenced by genetics, environment, and neurodevelopment. Left-handedness has a prevalence of 9–10% with variations based on ancestry. While hand dominance is evident at 6 months of age for most children and appears present at 18 weeks of gestational age or earlier, few studies have evaluated its association with brain asymmetries and their neurodevelopmental trajectories. Studies on functional connectivity and handedness have been limited, with one study reporting weaker interhemispheric connectivity between left M1 and right premotor area in adult left-handers than in right-handers. The specific patterns of functional connectivity associated with handedness in general and their emergence during childhood are mostly unknown. This study used the ABCD study to investigate the effects of handedness on brain structure during childhood. The large and diverse sample from the ABCD study also provided an opportunity to investigate the reproducibility of the effects of handedness on brain structure and function. The study selected 1800 children, comprising 600 left-handed, 600 right-handed, and 600 mixed-handed individuals. The selection ensured matching for sex, age, race, scanner manufacturer, family income, head motion, and total brain volume across the three groups. This sample size was carefully chosen to facilitate accurate participant matching and to enable a robust assessment of reproducibility. The study found that left-handedness is associated with increased functional connectivity in the left-hand motor area and reduced connectivity in the right-hand motor area, and with remarkable differences in the laterality of the connectivity of the motor cortex with sensory-motor regions, heteromodal cortical areas, and the cerebellum. The study also found that the effect of handedness on lateralization was highly reproducible across the Discovery and Replication subsamples. The study provides a simple neurobiological index of handedness that shows a strong correlation with handedness scores in children. The findings highlight distinct neural organizationsThis study investigates the relationship between handedness and brain functional connectivity patterns in 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. It finds that left-handers have increased global functional connectivity density (gFCD) in the left-hand motor area and decreased it in the right-hand motor area compared to right-handers. A connectivity-based index of handedness effectively differentiates right- and left-handers. The laterality of hand-motor connectivity varies across unimodal sensorimotor cortices, heteromodal areas, and the cerebellum, and is consistent across all regions of interest in the Discovery and Replication subsamples. The study shows a strong association between handedness and the laterality of functional connectivity patterns without differences in structural connectivity, brain morphometrics, or cortical myelin between left, right, and mixed-handed children. Handedness, the preference for using one hand over the other, is a trait associated with complex brain asymmetries influenced by genetics, environment, and neurodevelopment. Left-handedness has a prevalence of 9–10% with variations based on ancestry. While hand dominance is evident at 6 months of age for most children and appears present at 18 weeks of gestational age or earlier, few studies have evaluated its association with brain asymmetries and their neurodevelopmental trajectories. Studies on functional connectivity and handedness have been limited, with one study reporting weaker interhemispheric connectivity between left M1 and right premotor area in adult left-handers than in right-handers. The specific patterns of functional connectivity associated with handedness in general and their emergence during childhood are mostly unknown. This study used the ABCD study to investigate the effects of handedness on brain structure during childhood. The large and diverse sample from the ABCD study also provided an opportunity to investigate the reproducibility of the effects of handedness on brain structure and function. The study selected 1800 children, comprising 600 left-handed, 600 right-handed, and 600 mixed-handed individuals. The selection ensured matching for sex, age, race, scanner manufacturer, family income, head motion, and total brain volume across the three groups. This sample size was carefully chosen to facilitate accurate participant matching and to enable a robust assessment of reproducibility. The study found that left-handedness is associated with increased functional connectivity in the left-hand motor area and reduced connectivity in the right-hand motor area, and with remarkable differences in the laterality of the connectivity of the motor cortex with sensory-motor regions, heteromodal cortical areas, and the cerebellum. The study also found that the effect of handedness on lateralization was highly reproducible across the Discovery and Replication subsamples. The study provides a simple neurobiological index of handedness that shows a strong correlation with handedness scores in children. The findings highlight distinct neural organizations