Background : Low Birth Weight is a public health problem in Ethiopian. This study aimed to identify its determinant factors in Mekelle Zone, northern Ethiopia. Methods : Case control study design was employed on randomly selected 464 newborn. Baby measuring scale was used to weighing the newborn. Multivariable logistic regression was performed to identify the determinants factors, P < 0.05 and 95 % confidence level by using SPSS version 20 statistical software. Results : Maternal age <20 years (AOR = 2.9, 95 % CI: 1.55, 5.47), income < 2500 Ethiopian birr (AOR = 3.5, (95 % CI: 1.57, 7.95), gestation < 37 weeks (AOR= 4, 95% CI: 2.18, 7.29), hypertension (AOR= 2.6, 95% CI: 1.15, 6.07), anemia (AOR= 3.2, 95% CI: 1.70, 6.17), didn’t consume milk/week (AOR= 2.3, 95% CI: 1.02, 5.35), low dietary diversity (AOR = 2.8, 95% CI: 1.22, 6.19), MUAC < 23 cm (AOR = 2.1, 95% CI: 1.14, 4.04) were the identified determinants factors for low birth weight. Conclusions : Maternal age, income, history of hypertension and anemia, milk consumption, dietary diversity and maternal MUAC were the determinants Therefore, employing multisectoral coordinated intervention is essential to ending low birth weight.