The data from a randomly selected sample of 545 middle and high school-aged adolescents across the state of Iowa were studied to examine the means through which social stress is associated with depressive symptoms. Social stress is assumed to be socially determined by unjust social distributions of power and resources that place certain individuals and groups under greatest social pressure and give rise to situations that limit their access to already limited resources, obstruct alternative behavior options, and create unjustified interpersonal tension. Four variables were used to measure social stress: (1) lack of job opportunities, (2) competition in school, (3) gender discrimination in school, and (4) physical abuse. The negative effects of these variables of social stress on adolescents' mental health and well being were hypothesized to be moderated by the buffering effects social support and locus of control. The important findings are: (1) Lack of job opportunities, competition and physical abuse have significant positive effects on depression. (2) Social support and locus of control have significant negative effects on depression. (3) The moderating effects of social support and locus of control between depression and the variables of social stress are found to be significant. (4) There are significant gender differences between boys and girls. Lack of job opportunities and competition in school are more important in predicting depression for boys. Gender discrimination in school, physical abuse, and locus of control are more important in predicting depression for girls. (5) The proposed structural equation model explains more variance of depression for girls than for boys.