Background Young women and adolescent girls experience many challenges in their lives related to sanitation, hygiene, and menstruation. These challenges are often seen in a school setting and are more intense in peri-urban areas, where the infrastructure in educational institutions is often outpaced by the population, generating poor sanitary conditions. This can lead to adolescent girls contracting reproductive tract infections, such as candidiasis, as a result of poor menstrual hygiene. This study assessed menstrual hygiene management among students at a senior high school in the Volta Region, Ghana, in order to identify improvements to be made by school authorities to improve the health and comfort of students during menstruation. Methods This cross-sectional, descriptive study was conducted among 265 students aged 13–22 years, who had attained menarche. A pretested, structured questionnaire was used to collect data on their menstruation knowledge and practices, and the available sanitary facilities for menstrual hygiene management in the school. This was followed by an evaluation of the available facilities using a survey process. The Pearson chi-squared test was used to test the association between a student's year group and their knowledge and practices. Results The majority of the girls had accurate knowledge on menstruation (52.8% reported the correct length of a woman's menses, 74.7% correctly reported that a woman's menses comes once a month). However, the majority (63%) of participants reported the belief that menstrual blood is unhygienic and this belief was significantly associated with year group (P<0.00). When reporting on their practices during menstruation, the majority (76.2%) bathed twice a day and most (47.2%) changed their sanitary product twice a day. The frequency of these practices was significantly associated with year group (P=0.017 and P≤0.00, respectively). Only one-third (33.6%) of girls reported always having access to water for washing when menstruating and only 24.9% reported always having access to soap. The survey of facilities revealed that there was no handwashing facility in the school. Conclusions There is a need for Ghanaian educational institutions to provide proper sanitary facilities and for parents to provide sanitary pads or towels, which will allow girls who are menstruating to be comfortable and free of reproductive health infections. To achieve this, school authorities should be educated on the importance of providing the necessary sanitary facilities and parents should be educated on the necessity of provision of sanitary pads.