Rising mortality due to suicides, overdoses, and substance-related diseases, also called “deaths of despair,” has attracted significant academic, public, and media attention in recent years. This type of mortality, and key precursor “diseases of despair” like depressive mood and substance-related problems, tend to concentrate in people affected by deindustrialization and the loss of well-paid industrial jobs, that is, working-age adults with less than a BA degree. It is thought that risks build up when young adults with less education struggle to find decent jobs upon entering the labor market, which in turn triggers (1) subjective perceptions of being stuck in lower socioeconomic rungs; and (2) exposure to chronic stressors in various domains (e.g., housing, relationships). This study examined whether wages were related to diseases of despair (i.e., depressive mood and substance-related problems) through these two types of processes in a longitudinal sample (N = 543) overrepresenting young Canadian adults with lower educational attainment followed from their mid-teens to their mid-20s. Psychological processes and outcomes were self-reported, whereas exposure to stressors was assessed with a gold-standard interview-based protocol. After taking into account key potential confounders measured in adolescence (e.g., stressor exposure, mental health symptoms), results show that wages in early adulthood (in the early and mid-20s) were indirectly associated with depressed mood and substance-related problems in the mid-20s, through internal psychological processes and external exposure to chronic stressors. The specific processes in play varied by outcome. For depressive mood, subjective perceptions of one's relative socioeconomic position emerged as particularly relevant, whereas for substance-related problems, significant indirect associations emerged only when both internal psychological processes and external exposures to stressors were considered jointly. Access to decent jobs offering good wages among young adults without university degrees should thus be considered when designing policies aimed at reducing diseases of despair in younger generations.