Summary Background Seasonal influenza vaccine (SIV) uptake among US adults aged 65 years or older remains suboptimal and stagnant. Further, there is growing concern around racial and ethnic disparities in uptake. We aimed to assess racial and ethnic disparities in overall SIV and in high-dose vaccine (HDV) uptake among Medicare beneficiaries during the 2015–16 influenza season and sought to identify possible mediators for observed disparities. Methods We did a historical record-linkage cohort study using Medicare (a US national health insurance programme) databases, which included all older adults (≥65 years) enrolled in Medicare during the study period (July 1, 2015, to June 30, 2016). We excluded beneficiaries of Medicare Part C (managed care offered by private companies), and residents of long-term care facilities. The primary outcome was SIV receipt during the study period, classified into receipt of HDV and standard-dose vaccines (SDVs, representing all other SIVs). SIV uptake probabilities were estimated using competing-risk survival analysis methods. Mediation analyses were done to investigate potential mediators of the association between race and ethnicity and uptake. Findings During the study period, of 26·5 million beneficiaries in the study cohort, 47·4% received a SIV, 52·7% of whom received HDV. Compared with white beneficiaries (49·4%), Hispanic (29·1%), Black (32·6%), and Asian (47·6%) beneficiaries were less likely to be vaccinated and, when vaccinated, were less likely to receive HDV (37·8% for Hispanic people, 41·1% for Black people, and 40·3% for Asian people, compared with 53·8% of white people who received HDV). Among those vaccinated, after accounting for region, income, chronic conditions, and health-care use, minority groups were 26–32% less likely to receive HDV, relative to white people (odds ratio [OR] 0·68 [95% CI 0·68–0·69] for Black people; OR 0·71 [0·71–0·72] for Asian people; and OR 0·74 [0·73–0·74] for Hispanic people). Interpretation Substantial racial and ethnic disparities in SIV uptake among Medicare beneficiaries aged 65 years or older are evident. New legislative, fiscal, and educational strategies are urgently needed to address these inequities. Funding Sanofi Pasteur.