There are over 3 million truck drivers employed in the commercial transportation and material moving occupations, one of the largest occupational groups in the United States. Workers in this large and growing occupational segment are at risk for a range of occupational health-induced conditions, including mental health and psychiatric disorders due to high occupational stress, low access and use of health care, and limited social support. The purpose of this study was to explore male truck drivers' mental health risks and associated comorbidities, using a cross-sectional and quantitative design. Data were collected from a random sample of 316 male truckers between the ages of 23 and 76 at a large truck stop located within a 100-mile radius of Greensboro, North Carolina, USA, using a self-administered 82-item questionnaire. Surveyed truckers were found to have significant issues affecting their mental health, such as loneliness (27.9%), depression (26.9%), chronic sleep disturbances (20.6%), anxiety (14.5%), and other emotional problems (13%). Findings have potential to help researchers develop interventions to improve the emotional and occupational health of truck drivers, a highly underserved population. Mental health promotion, assessment, and treatment must become a priority to improve the overall trucking environment for truckers, the transportation industry, and safety on US highways.