Purpose: This study aims to test the hypothesis that in addition to a direct effect of food environment on obesity, food environment is indirectly associated with obesity through consuming Mediterranean diet (MD). Design: Cross-sectional secondary data analysis. Setting: Nationwide community-dwelling residency. Sample: A total of 20 897 non-Hispanic black and white adults aged ≥45 years who participated in the REasons for Geographic and Racial Differences in Stroke study and completed baseline assessment during January 2003 and October 2007. Measures: The Modified Retail Food Environment Index (mRFEI; 0-100) was used as food environment indicator. The MD score (0-9) was calculated to indicate the dietary pattern adherence. Body mass index (BMI; kg/m2) was used to estimate obesity. Analysis: Path analysis was used to quantify the pathways between food environment, MD adherence, and obesity. Proper data transformation was made using Box–Cox power transformation to meet certain analysis assumptions. Results: The participants were from 49 states of the United States, with the majority (64.42%) residing in the South. Most of the participants were retired, female, white, married, having less than college graduate education, having annual household income ≤75 000, and having health insurance. The means of mRFEI was 10.92 (standard deviation [SD] = 10.19), MD score was 4.36 (SD = 1.70), and the BMI was 28.96 kg/m2 (SD = 5.90). Access to healthy food outlets (β =.04, P <.0001) and MD adherence (β =.08, P <.0001) had significant and inverse relationships with BMI, respectively. Mediterranean diet adherence mediated the relationship between food environment and obesity among a subpopulation who had an annual household income of <$75 000 (β = −.02, P =.0391). Conclusion: Population-tailored interventions/policies to modify food environment and promote MD consumption are needed in order to combat the obesity crisis in the United States.