On a daily basis, schoolgirls in low and middle-income countries discover blood on their clothing for the first time in school environments without toilets, water, or a supportive teacher, mentor, or role model to help them understand the changes happening in their bodies. This study aimed to examine the menstrual knowledge, sociocultural restrictions, and barriers to menstrual hygiene management in school environment among adolescent schoolgirls in a rural community. We collected quantitative data from 250 adolescent schoolgirls and qualitative data from thirty schoolboys and five schoolteachers in five Junior High Schools in the Kumbungu district of northern Ghana. Binary logistic regression models were fitted to determine the predictors of poor menstrual knowledge. Qualitative data were transcribed verbatim, coded, and organized into themes. Overall, 53.6% of the girls had poor knowledge about menstruation. Most of the boys had heard about menstruation and had an idea about what menstruation is with most of them describing it as “the flow of blood through the vagina of a female.” The boys revealed that terms such as “Vodafone,” “Red card,” and “Palm oil” are used to describe menstruation in the schools and within the community. After adjusting for the effect of other sociodemographic factors, we found evidence that girls in their late adolescents were less likely to have poor menstrual knowledge compared to those aged 10–14 years (aOR 0.20, 95%CI 0.08–0.48). Maternal education was protective against poor menstrual knowledge. When compared to adolescents whose mothers were illiterates, those whose mothers had basic education (aOR 0.62, 95%CI 0.28–1.40) and those whose mothers had secondary or higher education (AOR 0.22, 95%CI 0.06–0.76) were less likely to have poor knowledge about menstruation. Adolescents from homes with no television and radio sets were more likely to have poor menstrual knowledge compared to those from homes with television and radio sets (aOR 2.42, 95%CI 1.41–4.15). Comfort, safety, and cost were the major factors that influenced their choice of sanitary products. Most of the teachers said the schools do not provide students with sanitary products, even in emergencies. We found that girls were not to prepare some local dishes (e.g. Wasawasa) during their periods and are forbidden from participating in religious activities (i.e. read the Holy Quran or pray in the mosque) during the period of menstruation. Open discussions about menstruation and its management are not encouraged and girls are considered unclean and impure during the period of menstruation. None of the schools had a regular supply of water in WASH facilities, a mirror for girls to check their uniforms for bloodstains or soap in the toilet facilities for handwashing. Menstrual education through the standard school curriculum, starting from primary school, could prepare girls for menarche, improve their knowledge on menstruation, and teach boys how to support girls and women during the period of menstruation. This could also eliminate the sociocultural misconceptions surrounding menstruation.