Abstract Background In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. Methods A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. Results Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. Conclusions Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.