Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social interaction, communication, and repetitive behaviors. Neuroimaging studies have revealed structural and functional neural changes in individuals with ASD compared to healthy subjects. Objectives: This study aimed to investigate brain network structural connectivity in ASD using Morphometric Similarity Network (MSN) analysis. Methods: Data from the Autism Brain Imaging Data Exchange (ABIDE) were analyzed, comprising 597 individuals with ASD and 644 healthy controls. Structural connectivity was assessed using cortical morphometric features. Global and regional network indices, including the density index, node degree, node strength, and clustering coefficients, were evaluated. Results: Among the global network indices, when using a threshold value of 0.4, ASD patients compared to HCs showed a lower density (p = 0.041) and higher negative clustering (p = 0.0051) coefficients. For regional network indices, ASD patients showed a lower bilateral superior frontal cortices degree (left hemisphere: p = 0.014; right hemisphere: p = 0.0038) and strength (left: p = 0.017; right: p = 0.018). Additionally, they showed higher negative clustering coefficients in the bilateral superior frontal cortices (left, p = 0.0088; right, p = 0.0056) and bilateral pars orbitalis (left, p = 0.016; right, p = 0.0006), as well as lower positive clustering in the bilateral frontal pole (left, p = 0.03; right, p = 0.044). Conclusions: These findings highlight significant alterations in both global and regional brain network organization in ASD, which may contribute to the disorder’s cognitive and behavioral manifestations. Future studies are needed to investigate the pathophysiological mechanisms underlying these structural connectivity changes, to inform the development of more targeted and individualized therapeutic interventions for individuals with ASD.