Local chicken enterprises in Africa are of great importance to household livelihoods but face major constraints with devastating disease outbreaks such as Newcastle disease (ND), which cause major economic losses. A study was conducted in two countries, Ghana and Tanzania, where three ecotypes in each country were challenged with a lentogenic (vaccine) strain of ND virus and various response phenotypes, including growth, anti-NDV antibody levels, and viral load from hatch to 38 days of age were taken. We estimated variance components and performed a genome-wide association study (GWAS) using ~2800 birds. Moderate heritabilities (0.14-0.55) of the above traits indicated that selection to improve these breeds/ecotypes for resistance to ND could be feasible. Genome-wide association analyses revealed several genomic regions that explained more than 0.5% of the genetic variance, including a candidate gene region for antibody response on chromosome 1. Future studies will characterize differences between the breeds/ecotypes, determine if large breed-specific quantitative trait loci can be identified, and evaluate the response of the same birds to endemic, velogenic ND virus strains.