Introduction: Socioeconomic status (SES) in childhood and beyond may influence the gut microbiome (GMB), with implications for disease risk. Studies evaluating the relationship between life-course SES and the gut microbiome (GMB) are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SES. Hypothesis: Low life-course SES indicators are associated with less diversity and overall composition of the gut microbiome in United States (U.S.) Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multi-site population-based cohort study conducted in the U.S. Childhood sanitation conditions (plumbing, sewer/septic tank), childhood SES (parental education and childhood hardship), adulthood neighborhood SES, and adulthood SES (education, income, and economic hardship) were used as life-course SES indicators. Shotgun sequencing was performed on stool samples (n=1057). Alpha-diversity was measured by the Shannon diversity index. Permutational multivariate analysis of variance was used to assess the association of SES indicators with overall microbiome composition, as measured using the Jensen-Shannon Divergence distance. Analysis of Compositions of Microbiomes was used to identify associations of life-course SES indicators with GMB species, adjusting for age, sex, BMI, U.S. or foreign-born, study center, Hispanic/Latino background, type of stool, diet quality, smoking, alcohol consumption, depressive and anxiety symptoms, diabetes, hypertension, cardiovascular disease, dyslipidemia, and antibiotic use. Results: Low sanitation and low SES during childhood were reported by 32% (342 of 1053) and 37% (330 of 884) of participants, respectively. In adulthood, 56% (585 of 1053) lived in a low SES neighborhood and 45% (447 of 1002) had low SES. Life-course SES indicators were not associated with GMB diversity. However, overall microbiome composition differed significantly according to childhood SES (R2 =0.28%, P = 0.04). Low childhood sanitation was associated with higher abundance of Ruminococcus torques and Clostridium lactatifermentans , and depleted abundance of Prevotella species. Low childhood SES was associated with higher abundance of species from genus Streptococcus (S. salivarius, S. parasanguinis, and S. infantis), Veillonella parvula, Prevotella stercorea, and Roseburia intestinalis. Low adulthood SES was associated with depleted abundance of species from Bacteroides, and living in a low adulthood neighborhood SES was associated with depleted abundance of species from Rikenella . Conclusion: Low childhood SES was associated with an altered GMB composition in U.S. Hispanic/Latino adults. Early-life SES may have long-term effects on GMB composition, underscoring another biological mechanism linking early childhood factors to adulthood disease.