Introduction: Mothers/caregivers should be aware of a newborn’s danger signs and promptly seek medical attention. Hence, this study assessed mothers’/caregivers’ awareness, healthcare seeking behaviors for neonatal danger signs and their determinants in the developing regional state of Ethiopia.MethodsA community-based cross-sectional study was employed among mothers/caregivers of neonates in the developing regional state of Ethiopia. The sample was determined in collaboration with the Central Statistics Agency of Ethiopia. Stratified multi-stage cluster sampling was used to recruit the sample. Data were collected through an interviewer administered structured questionnaire using a tablet computer. Descriptive statistics and binary logistic regression were applied to identify determinants of awareness and treatment-seeking behavior for neonatal danger signs.ResultsThe result of the study showed that nearly one-third (32.7%) of the respondents had a good level of awareness of neonatal danger signs, and 69.0% of the respondents had good healthcare-seeking practice about neonatal danger signs. Regional state (Benishangul-Gumuz) [AOR = 1.61; 95% CI (1.09, 2.39)], Muslim’s [AOR = 1.75; 95% CI (1.20, 2.55)] and permission to travel to a health facility [AOR = 0.48; 95% CI (0.37, 0.63)] were determinants of mothers’/caregivers’ awareness about neonatal danger signs. Antenatal care (ANC) attendance and institutional delivery were shown to have a positive association with neonatal healthcare seeking (AOR = 2.14 and AOR = 2.37, respectively).ConclusionIn Ethiopia’s developing regional states, mothers/caregivers were remarkably unaware of neonatal danger signs. Region, religion, mothers’/caregivers’ age, and need for permission to travel to a health facility were predictor variables for neonatal danger sign awareness. Better healthcare seeking practices, which are determined by ANC attendance and institutional delivery, are observed in these regions. Federal and regional governments should give these regions due attention. Moreover, regional health bureaus and health professionals should tackle the problem by focusing on the identified factors.