Objective Numerous studies have implicated the hippocampus and prefrontal cortex in schizophrenia. However, precisely which subregions of the hippocampus and prefrontal cortex are abnormal remain unknown. Our study goal was to investigate the structure of the anterior hippocampus, posterior hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) simultaneously in thirty-eight patients with schizophrenia and twenty-nine controls to determine which of these subregions are abnormal in schizophrenia. As an exploratory study goal, we investigated the relation of neurocognition to brain structure in schizophrenia patients. Method We generated detailed structural magnetic resonance imaging data and compared hippocampal and prefrontal subregional structural brain volumes between schizophrenia and control groups. We obtained a neurocognitive test battery in schizophrenia patients and studied the association of abnormal brain structures to neurocognition. Results Structural brain abnormalities were pinpointed to the left anterior hippocampus and left OFC in schizophrenia patients, which were both significantly reduced in volume. The DLPFC and posterior hippocampus, though numerically decreased in volume, were not significantly decreased. Anterior hippocampal volumes were more strongly associated with OFC volumes in schizophrenia patients compared to controls. By contrast, DLPFC volume was unrelated to anterior or posterior hippocampal volume. Both the anterior hippocampus and OFC were independently related to cognitive abnormalities common in schizophrenia, including indices of verbal, language, and executive functions. The DLPFC and posterior hippocampal volumes were unrelated to cognitive measures. Conclusions These findings highlight related abnormalities of the anterior hippocampus and OFC in schizophrenia, which may shed light on the pathophysiology of the disorder.