Runaway and homeless youth often have a constellation of background behavioral, emotional, and familial problems that contribute to stress and maladaptive behaviors, which, in turn, can lead to self-harming and suicidal behaviors. The current study examined the roles of stress and maladaptive behaviors as mediators between demographic and psychosocial background characteristics and self-injurious outcomes through the lens of the stress process paradigm. The model was tested in a sample of runaway and homeless youth from Los Angeles County (N = 474, age 12-24, 41% female, 17% White, 32.5% African American, 21.5% Hispanic/Latino). Background variables (gender, age, sexual minority status, parental drug use history, and emotional distress) predicted hypothesized mediators of maladaptive behaviors and recent stress. In turn, it was hypothesized that the mediators would predict self-harming behaviors and suicide attempts in the last 3 months. Females and LGBT (lesbian, gay, bisexual, transgender) youth were more likely to have self-harmed and attempted suicide; younger participants reported more self-harming. The mediating constructs were associated more highly with self-harming than suicide attempts bivariately, although differences were modest. Maladaptive behaviors and recent stress were significant predictors of self-harm, whereas only recent stress was a significant predictor of suicide attempts. All background factors were significant predictors of recent stress. Older age, a history of parental drug use, and greater emotional distress predicted problem drug use. Males, younger participants, and participants with emotional distress reported more delinquent behaviors. Significant indirect effects on self-harming behaviors were mediated through stress and maladaptive behaviors. The hypothesized paradigm was useful in explaining the associations among background factors and self-injurious outcomes and the influence of mediating factors on these associations.