IMPORTANCE Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed. OBJECTIVE To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023. EXPOSURE The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence. MAIN OUTCOMES AND MEASURES The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category. RESULTS Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB. CONCLUSIONS AND RELEVANCE The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.