Background The study was conducted in public health centers of East Gojjam Zone, Amhara region, Ethiopia. The purpose of this study was to assess knowledge, and use of labour pain relief methods and associated factors among obstetric caregivers in the study setting. Methods A facility-based cross-sectional study design was conducted from March 1–30, 2018. The study was conducted among three hundred and nine sampled obstetric caregivers. Structured questionnaire was used to collect the data. The data were entered into Epi-data version 4.2 Software for cleaning and exported to SPSS version 23.0 for data analysis. Multivariate logistic regression was carried out for variables with a p-value < 0.25 in bivariate logistic regression to determine significant relationships between the dependent and independent variables. Statistical significance was determined at 95% confidence interval (CI) and p-value below 0.05. Result The overall use of labour pain relief methods reported was 34.4%, (30.4% non-pharmacological and 8.4 pharmacological, respectively). More than half of the study participants (54.2%) had adequate knowledge about labour pain relief methods. In multivariate analysis, being a midwifery profession [AOR =2.814, 95% CI = (1.574–5.031)], having positive attitude [AOR = 4.370, 95% CI = (2.523–7.567)], and professionals with a medium level of education [AOR = 3.450, 95% CI = (1.993–5.971)] were factors significantly associated with knowledge of obstetric caregivers about labour pain relief methods. In multivariate analysis, knowledge of obstetric caregivers [AOR = 3.821, 95% CI = (2.091–6.980)], positive attitude of obstetric caregivers [AOR = 2.455, 95% CI = ((1.358–4.436))] and experience of obstetric caregivers [AOR = 2.56, 95% CI = (1.350–4.845) were factors significantly associated with the use of labour pain relief methods. Conclusion In this study, the overall use of labour pain relief methods by obstetric caregivers was low. Systemic opioid (Pethdine) was reportedly one of the most known pharmacological pain relief methods in this study. Providers’ knowledge, attitude and work experience had shown statistical significance with the use of labour pain relief methods. Task-oriented in- service training is required to fortify obstetric caregivers’ knowledge and attitude towards the use of labour pain relief methods.