The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43–0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.