It is estimated that since the beginning of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), nearly three million US military personnel have been deployed to Afghanistan and Iraq. Previous research has established that OEF/OIF military personnel are at increased risk for developing psychopathology after returning from deployment. Extant work has identified personality traits as unique factors associated with psychopathology among military personnel. Although most prior research has investigated the influence of personality traits on the development of psychopathology after returning from military deployment, little research has been conducted examining the influence of personality on the development of psychopathology during war-zone deployment. As such, the primary aim of the present study was to examine the influence of pre-deployment personality traits of the five-factor model (FFM) on the development of in-theater psychopathology among first-time deployed soldiers. We hypothesized that neuroticism would emerge as a risk factor, whereas extraversion, conscientiousness, openness to experience, and agreeableness would independently emerge as resilience factors, in the development of in-theater posttraumatic stress (PTSS), anxiety, and depressive symptoms. A total of 130 US soldiers completed a battery of pre-deployment assessments and monthly web-based self-report assessments of war-zone stressors during their deployment to Iraq. Multilevel models were used to examine the incremental main effects of each of the FFM personality traits on the subsequent emergence of in-theater PTSS, anxiety, and depressive symptoms. Results revealed that neuroticism emerged as a significant risk factor for PTSS. Similarly, openness to experience emerged as a significant risk factor, whereas conscientiousness emerged as a significant protective factor, for both anxiety and depressive symptoms. Extraversion and agreeableness demonstrated no significant effects across outcomes. Overall, the findings suggest that pre-deployment personality traits are associated with the emergence of PTSS, depression, and anxiety symptoms among OIF soldiers in the war-zone. To our knowledge, this is the first study to investigate the effects of personality and in-theater psychopathology among first-time deployed soldiers. As such, the current study contributes novel findings to the existing fields of personality and military research with potential important theoretical and clinical implications for military populations.