A phenomenon in schizophrenia patients that deserves attention is the high comorbidity rate with obsessive-compulsive disorder (OCD). Little is known about the neurobiological basis of schizo-obsessive comorbidity (SOC). We aimed to investigate whether specific changes in white matter exist in patients with SOC and the relationship between such abnormalities and clinical parameters. Twenty-eight patients with SOC, 28 schizophrenia patients, 30 OCD patients, and 30 demographically matched healthy controls were recruited. Using Tract-based Spatial Statistics and Probabilistic Tractography, we examined the pattern of white matter abnormalities in these participants. We also used ANOVA and Support Vector Classification of various white matter indices and structural connection probability to further examine white matter changes among the 4 groups. We found that patients with SOC had decreased fractional anisotropy (FA) and increased radial diffusivity in the right sagittal stratum and the left crescent of the fornix/stria terminalis compared with healthy controls. We also found changed connection probability in the Default Mode Network, the Subcortical Network, the Attention Network, the Task Control Network, the Visual Network, the Somatosensory Network, and the cerebellum in the SOC group compared with the other 3 groups. The classification results further revealed that FA features could differentiate the SOC group from the other 3 groups with an accuracy of .78. These findings highlight the specific white matter abnormalities found in patients with SOC.