Brain lesions may disturb hand functioning in children with cerebral palsy (CP), making it difficult or even impossible for them to perform several manual activities. Most conventional treatments for hand dysfunction in CP assume that reducing the hand dysfunctions will improve the capacity to manage activities (i.e., manual ability, MA). The aim of this study was to investigate the directional relationships (direct and indirect pathways) through which hand skills influence MA in children with CP. A total of 136 children with CP (mean age: 10 years; range: 6–16 years; 35 quadriplegics, 24 diplegics, 77 hemiplegics) were assessed. Six hand skills were measured on both hands: touch-pressure detection (Semmes–Weinstein esthesiometer), stereognosis (Manual Form Perception Test), proprioception (passive mobilization of the metacarpophalangeal joints), grip strength (GS) (Jamar dynamometer), gross manual dexterity (GMD) (Box and Block Test), and fine finger dexterity (Purdue Pegboard Test). MA was measured with the ABILHAND-Kids questionnaire. Correlation coefficients were used to determine the linear associations between observed variables. A path analysis of structural equation modeling was applied to test different models of causal relationships among the observed variables. Purely sensory impairments did seem not to play a significant role in the capacity to perform manual activities. According to path analysis, GMD in both hands and stereognosis in the dominant hand were directly related to MA, whereas GS was indirectly related to MA through its relationship with GMD. However, one-third of the variance in MA measures could not be explained by hand skills. It can be concluded that MA is not simply the integration of hand skills in daily activities and should be treated per se, supporting activity-based interventions.