Background <p>Postural control is often impaired in children with spastic cerebral palsy (sCP), with inter-individual differences not fully explained by CP topography or functional level. While brain lesion characteristics are known determinants of upper limb function, their predictive value for postural control remains underexplored.</p> Methods <p>In this cross-sectional study, 43 children with uni- or bilateral sCP (GMFCS I-III), aged 5–12 years, underwent standardized postural control assessment using the Kids-BESTest-2 (in percent scores). Lesion type was classified using the&#xa0;MRI classification scale (MRICS), and lesion extent and location were retrospectively scored on clinical MRI using the semi-quantitative MRI (sqMRI) scale. Associations between lesion characteristics and postural control domains were analyzed using stepwise regression models.</p> Results <p>Children with predominant white or grey matter lesions performed similarly across all postural control domains. Greater lesion extent was significantly associated with poorer postural control in all domains (<i>β</i> = –0.8 to –1.8% per sqMRI point increase, <i>p</i> ≤ 0.02) except ‘Sensory Orientation’. Lesions in the frontal lobe, anterior corpus callosum, PLIC, thalamus, and brainstem were the strongest predictors of domain-specific deficits, explaining up to 53% of variance.</p> Conclusion <p>Lesion extent and location, rather than type, determine the severity and domain-specificity of postural control deficits in sCP. Lesion-specific MRI scoring may support patient-tailored rehabilitation and prognosis.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>This study demonstrates that semi-quantitative MRI-based scoring of brain lesion extent and location, rather than lesion type, is key to understanding domain-specific postural control deficits in children with spastic cerebral palsy.</p> </ItemContent> <ItemContent> <p>It provides novel evidence that damage to specific brain regions, including the frontal lobe, anterior corpus callosum, PLIC, thalamus, and brainstem, most strongly predicts impairments in distinct postural control domains.</p> </ItemContent> <ItemContent> <p>Lesion-specific MRI profiling has clinical value for identifying postural control deficits and guiding individualized rehabilitation in children with spastic cerebral palsy. Further longitudinal and multimodal research is needed to validate these findings and optimize intervention strategies.</p> </ItemContent> </UnorderedList></p>