Objective Lack of proper menstrual hygiene predisposes women to different infectious and chronic obstetric and gynecological problems. A Facility based cross-sectional study was implemented from October 1- December 10, 2018. The data was collected using structured, pretested questioners among female high school students. Systematic random sampling technique was implemented. Data was entered and analyzed through Epi data 3.1 and SPSS respectively. Therefore, this study aimed to assess knowledge, attitude, practice and its associated factors of menstrual hygiene among high school students in North Wollo Zone, Woldia, Ethiopia. Results This study revealed that 365(89.2%), 200(48.9%) and 196(47.9%) of the study participants have good knowledge, good practice and good attitude about menstrual hygiene respectively. Being grade 10 students [AOR=3.96, 95% CI =2.0-7.8], and having good practice of menstrual hygiene (AOR=2.52, 95% CI= 1.26-5) had positive association with menstrual hygiene knowledge. Maternal education level (AOR=1.86, 95% CI=1.18-2.9), being grade 10 students (AOR =2.3, 95% CI=1.48-3.56) were associated factors for practicing menstrual hygiene. Being grade 10 students (AOR=1.9, 95% CI=1.2-2.8), age ≥18 years (AOR=1.67, 95% CI=1.09-2.55) were statistically and positively associated with the attitude of menstrual hygiene.