A cross-sectional study was conducted from February 2020 to December 2020 to determine the seroprevalence and associated risk factors of Newcastle disease in selected districts of Illubabor Zone, South-western Ethiopia. Districts were selected by convenient sampling method and PAs were selected randomly. A total of 384 serum samples were collected from chicken of greater than 3 weeks of age and a serological test was conducted using Indirect ELISA. The Indirect ELISA test identified the overall seroprevalence of avian paramyxovirus serotype-1 (APMV-1) 16.93% (65) (95% CI: 13.2-20.7%). This study estimated 12% (95% CI: 5.6-18.4%), 16.8% (95% CI: 10.1-23.5%), and 20% (13.9- 26.1%) seroprevalence of Newcastle disease in Hurumu, BiloNopa, and Metu districts respectively. Among the individual chicken risk factors assessed; sex (OR: 2.93, 95% CI: 1.35-6.38, P=0.007) and from flock level risk factors, flock size (OR=1.23, 95% CI=1.006-1.27, P=0.039) and disposal of dead chickens (OR: 11.67, 95% CI: 3.58-38.02, P<0.001) were significantly associated with seroprevalence of Newcastle disease. The results of the present study revealed higher seroprevalence of Newcastle disease in the study area and deserved the implementation of appropriate preventive and control measures and further studies should be undertaken to identify types of strains circulating in this area.