Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3–2.2), renal (OR, 1.6; 95% CI, 1.2–2.1), digital ischemia (OR, 1.5; 95% CI, 1.4–2.2), muscle (OR, 1.7; 95% CI, 1.3–2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1–9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4–2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0–1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.