Understanding relationships between individual-level demographic, socioeconomic status (SES) and U.S. opioid fatalities can inform interventions in response to this crisis. The Mortality Disparities in American Community Study (MDAC) links nearly 4 million 2008 American Community Survey responses to the 2008-2015 National Death Index. Univariate and multivariable models were used to estimate opioid overdose fatality hazard ratios (HR) and 95% confidence intervals (CI). Opioid overdose was an overrepresented cause of death among people 10 to 59 years of age. In multivariable analysis, compared to Hispanics, Whites and American Indians/Alaska Natives had elevated risk (HR = 2.52, CI:2.21-2.88) and (HR = 1.88, CI:1.35-2.62), respectively. Compared to women, men were at-risk (HR = 1.61, CI:1.50-1.72). People who were disabled were at higher risk than those who were not (HR = 2.80, CI:2.59-3.03). Risk was higher among widowed than married (HR = 2.44, CI:2.03-2.95) and unemployed than employed individuals (HR = 2.46, CI:2.17-2.79). Compared to adults with graduate degrees, those with high school only were at-risk (HR = 2.48, CI:2.00-3.06). Citizens were more likely than noncitizens to die from this cause (HR = 4.62, CI:3.48-6.14). Compared to people who owned homes with mortgages, those who rented had higher HRs (HR = 1.36, CI:1.25-1.48). Non-rural residents had higher risk than rural residents (HR = 1.46, CI:1.34, 1.59). Compared to respective referent groups, people without health insurance (HR = 1.30, CI:1.20-1.41) and people who were incarcerated were more likely to die from opioid overdoses (HR = 2.70, CI:1.91-3.81). Compared to people living in households at least five-times above the poverty line, people who lived in poverty were more likely to die from this cause (HR = 1.36, CI:1.20-1.54). Compared to people living in West North Central states, HRs were highest among those in South Atlantic (HR = 1.29, CI:1.11, 1.50) and Mountain states (HR = 1.58, CI:1.33, 1.88). Opioid fatality was associated with indicators of low SES. The findings may help to target prevention, treatment and rehabilitation efforts to vulnerable groups.