Newcastle disease (ND) is a real threat for commercial layer chicken farms in Bangladesh. However, only few studies have focused on exploring the epidemiology of this disease. A case-control study was conducted to identify determinants of Newcastle disease in commercial layer chicken farms in Kishoreganj and Gazipur district of Bangladesh between September 2019 and February 2020. Farms with birds diagnosed as ND positive based on clinical history, clinical signs and postmortem findings were considered as case and farms that did not have such ND positive chickens were the control for this study. Farmers of 56 case farms and 56 control farms were interviewed face to face using a structured questionnaire. The association between Farms’ ND status and determinants was assessed by multivariable logistic regression with backward elimination. In the final model, six variables were found to be associated with the risk for ND outbreak: age of the farmers (Odds Ratio [OR] 0.94; 95% Confidence Interval [CI] 0.87–0.99), distance from the nearest poultry farms (OR = 3.23, 95% CI 1.27–8.39), number of houses in the farms (OR = 3.06, 95% CI 1.06–8.83), surrounding environments (OR = 5.27, 95% CI 1.96–14.20), rearing different aged bird together (OR = 4.76, 95% CI 1.25–18.19), and no isolation of sick birds (OR = 2.85, 95% CI 1.07–7.55). Alteration of these determinants should reduce the ND burden in commercial layer chicken farms.