Malaria is a substantial health burden in Ghana, particularly among children. Despite the availability of malaria vaccines, uptake remains low. Notwithstanding, there is a paucity of nationally representative studies on the factors driving hesitance towards the new malaria vaccine. In response, this study, guided by the Theory of Planned Behaviors (TPB), seeks to understand the determinants of child malaria vaccine uptake in Ghana to inform strategies for improving coverage. We employed multiple regression model to examine the association between maternal awareness, socioeconomic status, ethnicity, geographical location, and vaccine uptake using data from the 2019 Ghana Malaria Indicator Survey (MIS). Maternal awareness of vaccine (OR = 2.200; P<0.01) significantly predicted higher likelihood of vaccine uptake. Household wealth was associated with child vaccination as parents in middle-income households (OR = 9.342; P<0.01), and those in poorest households (OR = 9.409; P<0.05) recorded higher likelihood of allowing their children to be vaccinated. With regards to ethnicity, parents from the Mande ethnic group (OR = 0.106; P<0.05) were less likely to allow their children to be vaccinated when compared to parents from the Akan ethnic group. Knowing that malaria is covered by National Health Insurance (OR = 2.407; P<0.05) was associated with higher likelihood of allowing child vaccination compared to not knowing. More so, geographical variations were observed as parents who lived in rural areas (OR = 0.254; P<0.05) were significantly less likely to allow vaccination of their children compared to those in urban areas. Enhancing awareness through education campaigns can improve child malaria vaccine coverage. Observing socioeconomic disparities in uptake and ensuring equitable access to vaccines are vital. Tailored strategies considering ethnic background and geographical location, can as well enhance acceptance of the vaccine. This study provides valuable insights for developing effective strategies to reduce the burden of malaria in children and improve coverage of uptake. This study underscores the need to improve parental awareness and the relevance of the vaccine in preventing child mortality.