Social difficulties during interactions with others are central to autism spectrum disorder (ASD). Understanding the links between these social difficulties and their underlying neural processes is a primary aim focused on improved diagnosis and treatment. In keeping with this goal, we have developed a multivariate classification method based on neural data acquired by functional near infrared spectroscopy, fNIRS, during live eye-to-eye contact with adults who were either typically developed (TD) or individuals with ASD. The ASD diagnosis was based on the gold-standard Autism Diagnostic Observation Schedule (ADOS) which also provides an index of symptom severity. Using a nested cross-validation method, a support vector machine (SVM) was trained to discriminate between ASD and TD groups based on the neural responses during eye-to-eye contact. ADOS scores were not applied in the classification training. To test the hypothesis that SVM identifies neural activity patterns related to one of the neural mechanisms underlying the behavioral symptoms of ASD, we determined the correlation coefficient between the SVM scores and the individual ADOS scores. Consistent with the hypothesis, the correlation between observed and predicted ADOS scores was 0.72 (p < 0.002). Findings suggest that multivariate classification methods combined with the live interaction paradigm of eye-to-eye contact provide a promising approach to link neural processes and social difficulties in individuals with ASD.