Background: During menstruation, school girls face obstacles connected to menstrual hygiene management in schools. Due to their monthly period, up to 20% of girls miss school globally, and one in ten will drop out entirely. Three hundred thirty-five million girls attended school without access to running water or soap. In Ethiopia, 67% of girls have no access to education on puberty and menstrual health; menstrual hygiene management continues to be one of the major problems among school girls. Thus, context-specific assessment of the practice may be useful in developing customized intervention approaches. Thus, the objective of the study was to assess practices of menstrual hygiene management and associated determinants among secondary school girls in East Hararghe, Ethiopia from 1 to 30 December 2020. Methods: A school-based cross-sectional survey was undertaken with 486 randomly selected female students. Data were collected by pretested self-administered questionnaire. Descriptive statistical tests and multivariate logistic regression were used to describe the study variables and to examine the association. Statistical package for social science version 23 was used for data analysis, and a p-value of 0.05 was considered as a cut-off point for statistical significance. Results: Of the total, 328 (68%) of the study participants practiced appropriate menstrual hygiene. Besides, 350 (72.6%) had a good level of understanding about menstrual hygiene. A higher level of knowledge (adjusted odds ratio = 2.12, 95% confidence interval = 1.28, 3.53), a greater wealth indexed family (adjusted odds ratio = 7.14, 95% confidence interval = 3.98, 12.88), earning permanent pocket money (adjusted odds ratio = 0.495, 95% confidence interval = 0.299, 0.821), and being in grade level (11–12) (adjusted odds ratio = 3.45, 95% confidence interval = 1.75, 4.501) were significant predictors of the good menstrual hygiene practice. Conclusion: One-third of the school girls had poor menstrual hygiene practices which may affect their school performance and the reproductive health. Hence, tailored menstrual hygiene information should be given to school girls and parents. Besides, efforts ought to be made for the provision of affordable sanitary materials in schools.