Abstract Background Menarche is an expected event that occurs during the development of every normal young girl. We designed this study to evaluate the knowledge of young school girls on puberty, menarche, and menstruation, and to update data on the age at menarche in a rural and urban setting in Cameroon. Methods We conducted a cross-sectional survey from February to March 2017, targeting female students aged 9 to 16 years in Yaoundé (urban) and Bamougoum (rural). Participants were included using a randomised cluster sampling and data collected using an auto-administrable questionnaire. Student t-test or the Kruskal-Wallis test was used to compare means, and the odds ratio used as the measure of association between age at menarche and selected covariates. Results 1157 participants were included in the study; 49.3% from an urban setting and 50.7% from a rural setting. Regarding the knowledge of our participants on puberty, menarche, and menstruation, 67.20% of rural participants had good knowledge, whereas only 46.00% had good knowledge in the urban setting. Mean age at menarche was 12.76 ± 1.33 years, with the mean age at menarche in the urban setting of 12.48 ± 1.12 years and the rural setting of 13.03 ± 1.46 years. Mean age at menarche was significantly lower in participants aged below 14 years (p-value = 0.000), those with both parents alive (p-value = 0.0461), those whose fathers had skilled occupations (p-value = 0.005), those of urban resident (p-value = 0.000), and those who watched TV everyday (p-value = 0.030). Urban residence and age below 14 years were significantly associated with an earlier onset of menarche. Conclusion Rural participants had better knowledge of puberty, menarche, and the menstrual cycle than their counterparts in the urban setting. The mean age at menarche over the last two decades has dropped by 7.4 and 4.2 months per decade in urban and rural Cameroon respectively. Mean age at menarche varies significantly with age group, urban/rural residence, state of both parents (both alive/at least one dead), occupation of the father, and frequency of watching TV. Age and urban/rural residence are associated with age at onset of menarche. The continually declining age at menarche is an alarm for future early menarche-linked morbidities.