Background In Ethiopia about 25% of rural women are chronically malnourished. Non-pregnant and non-lactating women present an opportunity to implement strategies to correct maternal and child health status and to potentiate improved pregnancy outcomes in developing countries like Ethiopia. The determinant factors of chronic energy deficiency vary across settings and contexts; hence, it is important to identify local determinant factors in order to implement effective and efficient intervention strategies. Objective To assess the determinants of chronic energy deficiency of non-pregnant, non-lactating rural women within the reproductive age group (15–49 years), in rural kebeles of Dera district, North West Ethiopia, 2019. Methods A community based unmatched case control study was conducted. A total of 552 participants were involved and a multi-stage sampling technique was used to select the samples. Data was collected from January 15 to February 30, 2019 using face-to-face interviews and anthropometric assessments. EPI-info version 7 and SPSS™ version 23 were used for data entry and analysis, respectively. Bivariable and multivariable logistic regression models were used to analyze the association between dependent and independent variables. Association was considered statistically significant at 95% CI with p-value < 0.05 in multivariable logistic regression. Result A total of 548 non-pregnant, non-lactating women with 137 cases and 411 controls were included in the study with a response rate of 99.3%. High family size (AOR = 1.88, 95% CI: 1.085, 3.275), low educational status (AOR = 3.389, 95% CI: 1.075, 10.683), inadequate meal frequency (AOR = 5.345, 95% CI: 2.266, 12.608), absence of home garden (AOR = 5.612, 95% CI: 3.177, 9.915) and absence of latrine facility (AOR = 6.365, 95% CI: 3.534, 11.462) were found positively associated with chronic energy deficiency. Conclusion and recommendation Inadequate meal frequency, absence of home gardening, absence of latrine facility, high family size and educational status of illiterate were the determinants of chronic energy deficiency, thus indicating the imperative for a multi-sectoral approach with health, agriculture and education entities developing and delivering interventions.