The prevalence and severity of depression differ in women and men and across racial groups. Psychosocial factors such as chronic stress have been proposed as contributors, but causes of this variation are not fully understood. Allostatic load, a measure of the physiological burden of chronic stress, is known to be associated with depression. Using data from the National Health and Nutrition Examination Survey 2005(-)2010, we examined the associations of nine allostatic load biomarkers with depression among US black and white adults aged 18(-)64 years (n = 6431). Depressive symptoms were assessed using the Patient Health Questionaire-9; logistic models estimated adjusted odds of depression based on allostatic load biomarkers. High-risk levels of c-reactive protein were significantly associated with increased odds of depression among white women (adjusted odds ratio (aOR) = 1.7, 95% CI: 1.1(-)2.5) and men (aOR = 1.8, 95% CI: 1.1(-)2.8) but not black women (aOR = 0.8, 95% CI: 0.6(-)1.1) or men (aOR = 0.9, 95% CI: 0.5(-)1.5). Among black men, hypertension (aOR = 1.7, 95% CI: 1.1(-)2.7) and adverse serum albumin levels (aOR = 1.7, 95% CI: 1.0(-)2.9) predicted depression, while high total cholesterol was associated with depression among black women (aOR = 1.6, 95% CI: 1.0(-)2.7). The associations between allostatic load biomarkers and depression varies with gendered race, suggesting that, despite consistent symptomatology, underlying disease mechanisms may differ between these groups.