Background: Neonatal mortality is still unacceptably high in Ethiopia. One key strategy to cut back neonatal mortality is increasing the mother's knowledge of neonatal danger signs and health-seeking practices. This study assessed mother's knowledge of neonatal danger signs and health-seeking practices and associated factors in Debretabor town, Northwest Ethiopia. Methods: A community-based cross-sectional study was conducted from July 1st to August 10th in Debretabor town, northwest Ethiopia and cluster sampling technique was used to select 772 mothers. A semi-structured, pretested and interviewer-administered questionnaire was employed. Data were entered into epi info version 7 and analyzed by SPSS 23. Multivariable logistic regression model was fitted to identify factors associated with' mother's knowledge of neonatal danger signs and health-seeking practices. Odds ratio with 95% confidence interval was computed to determine the level of significance. Results: Mother's knowledge of neonatal danger signs and health-seeking practices was 36.5% (95% CI: 33, 40) and 78.7% (95% CI: 72.9, 83.7) respectively. Media exposure (AOR=2.85; 95% CI: 1.47, 5.53), birth preparedness (AOR=9.06; 95% CI: 5.99, 13.7), husband involvement (AOR=1.45; 95% CI: 1.04, 2.11), increased parity (AOR=2.46; 95% CI: 1.16, 5.19), whose neonate developed danger signs (AOR=1.83; 95% CI: 1.25, 2.67) and higher educational status (AOR=2.88; 95% CI: 1.45, 5.69) were factors significantly associated with mother's knowledge of neonatal danger signs. Furthermore, having good knowledge of neonatal danger signs (AOR=4.0; 95% CI: 1.63, 9.8), being autonomous (AOR=4.35; 95% CI: 1.63, 11.6), media exposure (AOR=3.06; 95% CI: 1.08, 8.63), and husband involvement (AOR=3.53; 95% CI: 1.49, 8.33) were factors statically significant with health-seeking practices of mothers for neonatal danger signs. Conclusion: Our findings show that maternal knowledge of neonatal danger signs was low. Promotion of mother's decision-making power, birth preparedness, husband involvement and mass media throughout the maternal continuum of care will have a great role in improving mother's knowledge of neonatal danger signs and health-seeking practices.