On-road truckers face unique occupational stressors—long hours, irregular schedules, isolation, serious accident risk, and job insecurity—that can cumulatively increase vulnerability to depressive symptoms. While chronic stress is a well-documented risk factor for depression, the specific pathway through which occupational stress translates into depressive symptoms in this population remains underexplored. The purpose of a paper on the stress–depression pathway in on-road trucking is to explore the relationship between stress and depression in truck drivers, particularly in the context of their work environment. The paper aims to provide a conceptual model that explains how stressors related to trucking can lead to depression, and how understanding this relationship can inform interventions and support for truck drivers. The analysis of the conceptual model reveals that the influence of psychosocial stressors on fatigue and depressive symptoms in long-distance truck drivers (LDTD) contributes to depressive symptoms due to the body's inability to handle the stress effectively, leading to a cycle of negative mental health outcomes. In conclusion, the paper seeks to contribute to the body of knowledge in the field by offering insights into the psychological impact of trucking and by suggesting potential strategies to improve mental health among truck drivers. The paper concludes that understanding these interconnections is essential for developing effective strategies to support the mental health of long-distance truck drivers and reduce the prevalence of fatigue and depressive symptoms in this occupational group.