Background. Reproductive health (RH) is defined as a state of complete physical, mental, and social wellbeing and not merely the absence of disease or infirmity, in all matters related to the reproductive system and to its functions and process. Local evidence about adolescents’ reproductive health knowledge level and associated factors are relevant to design age-appropriate interventions strategies. Therefore, the aim of this study was to assess the knowledge level on reproductive health issues among secondary school students in Woldia town. Objective. The main aim of this study was to assess the knowledge level and associated factors among adolescents in Woldia secondary schools, Amhara, Ethiopia, 2019. Methods. Institution-based descriptive cross-sectional study was conducted on 420 secondary school students in Woldia town from January to June 2019. Multistage sampling technique was employed. A self-administered, structured, and adapted questionnaire was used to collect the data. The data was entered by using EpiData version 4.2 and exported to SPSS version 24.0 for analysis. The samples were distributed proportionally based on probability proportional to size (PPS) allocation technique. Participants in each school have been selected by using systematic sampling technique after calculating sample interval (K) for each school. Bivariate and multivariable logistic regressions were carried out to assess the association between dependent and independent variables. Result. The prevalence of good knowledge was 204 (48.6%). Residence, educational level, handling of RHS providers, ever gone RHS institution and missed RHS service, had RHS in school, and stigma to utilize RHS were found to be significantly associated with the level of knowledge of respondents on reproductive health issues. Conclusion and Recommendations. The knowledge of respondents on reproductive health issues in the study area was found to be low. Hence, it is better to improve access to information to the secondary school students on RHS through trained health workers and accessible RHS.