Background: Despite the significant investments to control malaria infection rates over the past years, infection rates remain significant in sub-Saharan Africa. This study investigates the association with use of large-scale malaria interventions such as: Indoor Residual Spraying (IRS), Insecticide Treated bed-Nets (ITN), and Behaviour Change Communication (BCC) strategies, and the prevalence of malaria among children under-five in Ghana. Methods: Cross-sectional data on 2, 449 children aged 6 to 59 months who were tested for malaria, through Rapid Diagnostic Test (RDT), are drawn from the recent wave of the Ghana Demographic and Health Surveys (GDHS 2014). We use a logit model to analyse the heterogeneous association between control measures and malaria infection among under five children of different age cohorts and household poverty statuses. Results: Our estimates suggest that IRS offers much more protection than ITN use. The odds of malaria infection among children who sleep in IRS is significantly lower (odds ratio [OR] = 0.312; 95% CI -1.47 -0.81; p = 0.00) compared to those who are not protected. This association is even high (odds ratio [OR] = 0.372; 95% CI -1.76 -1.02; p = 0.00) among children in poor households protected by IRS compared to those who have no IRS protection. ITN use did not have a significant association with malaria infection among children, except among children whose mothers have at least secondary education. For such children, the odds of malaria infection are significantly lower ([OR] =0.545; 95% CI = - 0.84 -0.11; p = 0.011) compared to those who are not protected. Regarding BCC strategies, we found that malaria education through television is the best strategy to covey malaria education as it significantly reduces the odds of malaria infection ([OR] =0.715; 95% CI = - 0.55 -0.10; p = 0.005) compared to those who do not received malaria education via television. BCC strategy via print media has a significant but limited protection for children of educated mothers. Conclusion: Policy makers should direct more resources to IRS, especially in communities where the use of ITN is less likely to be effective, such as poor and rural households. The distribution of ITNs needs to be accompanied with education programs to ensure its best protection.