Physically disabled persons continue to be discriminated, excluded and neglected based on design of structures and their location. This hampers equitable access to services and disproportionately affect them during a pandemic. This study aimed to evaluate physical access barriers to COVID-19 vaccines among persons with physical disabilities during the COVID-19 pandemic, (March 2020 to March 2022) in Ugenya Sub-county, Siaya County in Western Kenya. Methods The study design was cross-sectional. 108 physically disabled participants were selected using systematic sampling technique. Data was collected using structured questionnaires. Results Vaccination location (χ2=95.480, p=0.001), access to the vaccination room (χ2=84.098, p=0.001) and mobility impaired (χ2 = 16.168, p=0.001) had statistically significant associations with uptake of COVID-19 vaccine. Income levels, belief in existence of COVID-19, information from mass media and being married increased the odds of becoming vaccinated (AOR=1.5, 95% CI 0.7–3.4), (AOR=1.8, 95% CI 0.8-4.0) (AOR=2.5, 95% CI 1.5–4.2) and (AOR=2.2, 95% CI 1.3–3.9) respectively. The binary logistic regression analysis showed that transport cost and age (p=0.001) had statistically significant associations with COVID-19 vaccine access and uptake. Those who had difficulty in movement and speaking found uptake of COVID-19 vaccine hard (p=0.001). Conclusion Marital status, information from reliable sources, belief in existence of COVID-19 were associated with access to and uptake of COVID-19 vaccine. Additionally, nonpayment of transport cost increased the odds of becoming vaccinated. Therefore, mobile health teams should be put in place to reach the physically disabled who are hard-to-leave home. Additionally, reimbursement of amount spent on transportation can be adopted to boost access to healthcare services by the physically disabled persons.