Introduction: Multivariate machine learning methods can be used to classify groups of schizophrenia patients and controls using structural magnetic resonance imaging (MRI). However, machine learning methods to date have not been extended beyond classification and contemporaneously applied in a meaningful way to clinical measures. We hypothesized that brain measures would classify groups, and that increased likelihood of being classified as a patient using regional brain measures would be positively related to illness severity, developmental delays and genetic risk. Methods: Using 74 anatomic brain MRI sub regions and Random Forest, we classified 98 COS patients and 99 age, sex, and ethnicity-matched healthy controls. We also used Random Forest to determine the likelihood of being classified as a schizophrenia patient based on MRI measures. We then explored relationships between brain-based probability of illness and symptoms, premorbid development, and presence of copy number variation associated with schizophrenia. Results: Brain regions jointly classified COS and control groups with 73.7% accuracy. Greater brain-based probability of illness was associated with worse functioning (p= 0.0004) and fewer developmental delays (p=0.02). Presence of copy number variation (CNV) was associated with lower probability of being classified as schizophrenia (p=0.001). The regions that were most important in classifying groups included left temporal lobes, bilateral dorsolateral prefrontal regions, and left medial parietal lobes. Conclusions: Schizophrenia and control groups can be well classified using Random Forest and anatomic brain measures, and brain-based probability of illness has a positive relationship with illness severity and a negative relationship with developmental delays/problems and CNV-based risk.