Background Traditional neonatal uvulectomy is unsupervised, unscientific and potentially dangerous cultural malpractice. This malpractice is often accompanied with life threatening neonatal morbidities such as infection, anemia, aspiration and oropharyngeal injury. However, there is no current regional and even national data about the burden, associated factors and perception of traditional uvulectomy among neonatal admissions to neonatal intensive care units. Methods A quantitative cross sectional study supplemented with phenomenological study was employed on 422 mother-neonate pairs admitted to Debre Tabor General Hospital from September 2018 to August 2019. Eight women who were not included in the quantitative part were involved for the qualitative study. Systematic and purposive sampling methods were used to select study participants for the quantitative and qualitative study respectively. Binary logistic regression models were fitted to declare statistical significance at p-value ≤ 0.05 and 95% CI. Result Complications of traditional uvulectomy contributed 15.90% of the overall neonatal admissions. At admission, most of the victim neonates had septic presentation (88.1%) followed by anemia (55.2%). From multivariable analysis, having male neonate [AOR= 4.87; 95% CI: 1.10, 21.59], antenatal couple counseling about traditional neonatal uvulectomy [AOR=0.053; 95% CI: 0.01, 0.35], home delivery [AOR= 6.02 ; 95% CI: 1.15, 31.61], postnatal couple counseling about traditional neonatal uvulectomy [AOR= 0.101; 95% CI: 0.02, 0.65], prior history of traditional neonatal uvulectomy [AOR= 7.15; 95% CI: 1.18, 43.21] and knowing at least one disadvantage of traditional neonatal uvulectomy [AOR= 0.068; 95% CI: 0.01, 0.44] were independent predictors of the malpractice. Furthermore, maternal perception of no modern medicine to treat elongated uvula was the most explained reason to do the malpractice. Conclusion The burden of traditional uvulectomy was high. Fortunately, its predictors are modifiable. Therefore, different community groups including women health development armies, elders, religious fathers, health professionals and criminal prosecutors should be actively mobilized against this malpractice. Besides, parental couple counseling about the key message of no traditional neonatal uvulectomy should be properly implemented in the routine antenatal and postnatal programs of the health care delivery system at south Gondar zone.