Universal primary and secondary education is a key target of the Sustainable Development Goals. While substantial gains have been made at the primary school level, progress towards universal secondary education has slowed, particularly in sub-Saharan Africa. In this study, we aimed to determine perceived barriers of secondary schooling in rural Burkina Faso, where secondary school completion is among the lowest globally (<10%). We conducted a two-stage qualitative study using semi-structured interviews (N = 49). In the first stage, we sampled enrolled students (n = 10), out-of-school adolescents (n = 9), parents of enrolled students (n = 5), parents of out-of-school adolescents (n = 5) and teachers (n = 10) from a random sample of five secondary schools. In a second stage, we interviewed key informants knowledgeable of the school context using snowball sampling (n = 10). Systematic analysis of the pooled sample was based on a reading of interview transcripts and coding of the narratives in NVivo12 using the diathesis-stress model. Recurring themes were classified using a priori developed categories of hypothesized barriers to secondary schooling. Major reported barriers included school-related expenses and the lack of school infrastructure and resources. Insufficient and heterogeneous French language skills (the official language of instruction in Burkina Faso) were seen as a major barrier to secondary schooling. Forced marriages, adolescent pregnancies, and the low perceived economic benefits of investing in secondary schooling were reported as key barriers among young women. Our results guide future interventions and policy aimed at achieving universal secondary education and gender equity in the region.