BackgroundPersons with disabilities (PWD) are often marginalized and face barriers to accessing health services. This study aimed to examine the COVID‐19 vaccine uptake and its predictors among PWDs in the Ashanti region of Ghana, where about 17% of the population has some form of disability.MethodsA cross‐sectional survey was conducted among 402 PWDs in two districts of the Ashanti Region of Ghana from December 2021 to March 2022. Data were collected using a pretested structured questionnaire and analyzed using descriptive (frequencies and percentages) and inferential statistics (binary logistic regression).ResultsThe majority (68.7%) of the respondents had received the COVID‐19 vaccine. The vaccine uptake was significantly higher among PWDs with visual impairments (aOR = 1.81; 95% CI = 1.07–3.09; p = 0.028), older age groups (aOR = 4.95; 95% CI = 1.86–13.21; p = 0.001 for those aged 60 and above), those with junior high school level of education (aOR = 2.21; 95% CI = 1.05–4.64; p = 0.036), and those who were employed (aOR = 2.07; 95% CI = 1.07–3.99; p = 0.031), compared to their respective reference groups.ConclusionThe study revealed a moderate level of COVID‐19 vaccine uptake among PWDs in the Ashanti region, which may indicate some positive attitudes towards the prevention of the virus. However, there were disparities in the vaccine uptake by disability type, age, education, and employment status, which suggest the need for tailored interventions to address the specific needs and preferences of different subgroups of PWDs. The study also provides a basis for further research on the factors influencing COVID‐19 vaccine acceptance among PWDs in Ghana and other similar settings. To enhance the vaccine coverage and equity among the marginalized groups in the region, more practical and inclusive strategies are needed to overcome the barriers and challenges faced by PWDs in accessing the COVID‐19 vaccine.