(1) Background: Hydrocephalus poses challenges in pediatric neuroimaging, and conventional MRI methods have limitations regarding its accurate quantification. Synthetic MRI (SyMRI) offers a promising automated solution to assess intracranial compartment volumes. However, its clinical utility in pediatric patients remains underexplored. Our study aims to assess the accuracy and reliability of automated CSF volume measurements using SyMRI in children and adolescents, comparing them with manual measurements and human expert ratings. (2) Methods: A single-center retrospective study included 124 pediatric patients undergoing cranial MRI with SyMRI. CSF, brain parenchyma, and intracranial volumes were measured using both automated SyMRI and manual methods. Human radiologists assessed hydrocephalus subjectively. (3) Results: Correlations between manual and SyMRI volume evaluations were significant. Human raters demonstrated good agreement on hydrocephalus ratings among themselves (Fleiss’ kappa = 0.66, p < 0.001) but only moderate agreement with the SyMRI method (Cohen’s kappa = 0.45, p < 0.001). SyMRI volumes were systematically tendentially higher in SyMRI (CSF p = 0.005; BPV and ICV p < 0.001). (4) Conclusions: Our findings highlight SyMRI’s reliability in assessing hydrocephalus and intracranial volumes in pediatric cases. Despite some differences from manual measurements, the strong correlation suggests its clinical viability.