Background: Globally, more than 20.5 million infants are born with low birth weight, and the majorities were from Asia and Africa. Even though efforts were made to reduce low birth weight worldwide, it remains a global public health problem, especially in sub-Saharan Africa. Objective: To assess low birth weight and associated factors among newborn babies in health institutions in Dessie, Amhara, Ethiopia. Methods: An institution-based cross-sectional study was conducted among 358 newborn/ mother pairs from March 1 to April 15, 2017, in Dessie town health institutions. The data were collected using a semi-structured interviewer-guided questionnaire. The numbers of newborn/mother pairs surveyed from each health institution were allocated proportionally, and systematic random sampling was used to select the respondents. Epi-info version 7.0 was used for data entry, and Statistical Package for Social Sciences version 20 was used for the analysis. Multivariate logistic regression with adjusted odds ratios and 95% confidence intervals were used to identify significantly associated variables with low birth weight. Results: In this study, the prevalence of low birth weight was 15.6%. Maternal age <20 years (AOR: 3.78, 95% CI, 1.02-13.97), rural residence (AOR: 3.49, 95% CI, 1.48-8.24), having antenatal care follow-up (AOR: 3.79, 95% CI, 1.08-13.23), gestational age <37 weeks (AOR: 3.82, 95% CI, 1.55-9.42), and females (AOR: 3.37, 95% CI, 1.17-9.72) were significantly associated with low birth weight. Conclusion: The proportion of LBW in this study is comparable to the estimated global prevalence. Maternal age, residence, antenatal care, gestational age, and sex were significantly associated variables with low birth weight. Therefore, special attention should be given to antenatal care services and preventive strategies for preterm delivery.