Increased misinformation circulating among the population during the COVID-10 pandemic can trigger rejection to take up vaccines. This study assesses the influence of vaccine information and other factors on vaccine acceptance in the Thai population. Between March and August 2021, six rounds of cross-sectional surveys through village health volunteer networks and online channels were conducted; as well as qualitative interviews with frontline health workers, patients with chronic diseases, and religious believers and leaders. Descriptive and multiple logistic regression with 95% level of confidence were used for survey findings while deductive thematic analysis was used for in-depth interview findings. Among the total 193,744 respondents, the initial COVID-19 vaccine acceptance rate decreased from 60.3% in March 2021 to 44.0% in April 2021, then increased to 88.8% in August 2021. Participants who were able to differentiate true and false statements were 1.2 to 2.4 times more likely to accept vaccine than those who were not. Those who perceived a high risk of infection (Adjusted odds ratio; AOR = 2.6–4.7), perceived vaccine safety (AOR = 1.4–2.4), judged the importance of vaccination (AOR = 2.3–5.1), and had trust in vaccine manufacture (AOR = 1.9–3.2) were also more likely to accept the vaccine. Moreover, higher education (AOR = 1.6–4.1) and living in outbreak areas (AOR = 1.4–3.0) were significantly related to vaccine uptake, except in people with chronic diseases who tended not to accept the vaccine (AOR = 0.7–0.9). This study recommends effective infodemic management and comprehensive public communication, prioritising vulnerable groups such as those with a low level of education and people with chronic conditions. Communication through reliable channels can support higher vaccine acceptance and rapid vaccine rollout. Finally, regular monitoring of misinformation is important such as fact checking support, timely legal actions and specific debunking communication.