Background Compared to other racial/ethnic groups, infant mortality rates (IMR) are persistently highestamong Black infants in the United States, yet there is considerable regional variation. We examined state and county-level contextual factors that may explain regional differences in Black IMR and identified potential strategies for improvement. Methods and findings Black infant mortality data are from the Linked Birth/Infant Death files for 2009-2011. State and county contextual factors within social, economic, environmental, and health domains were compiled from various Census databases, the Food Environment Atlas, and the Area Health Resource File. Region was defined by the nine Census Divisions. We examined contextual associations with Black IMR using aggregated county-level Poisson regression with standard errors adjusted for clustering by state. Overall, Black IMR varied 1.5-fold across regions, ranging from 8.78 per 1,000 in New England to 13.77 per 1,000 in the Midwest. In adjusted models, the following factors were protective for Black IMR: higher state-level Black-White marriage rate (rate ratio (RR) per standard deviation (SD) increase = 0.81, 95% confidence interval (CI):0.70-0.95), higher state maternal and child health budget per capita (RR per SD = 0.96, 95% CI:0.92-0.99), and higher county-level Black index of concentration at the extremes (RR per SD = 0.85, 95% CI:0.81-0.90). Modeled variables accounted for 35% of the regional variation in Black IMR. Conclusions These findings are broadly supportive of ongoing public policy efforts to enhance social integration across races, support health and social welfare program spending, and improve economic prosperity. Although contextual factors accounted for about a third of regional