Spoken lessons (lectures) are commonly used in schools as a medium for conveying educational content. In adolescence, experience-expectant maturation of language and cognitive systems supports learning; however, little is known about whether or how learners' language experiences interact with this integration process during learning. We examined functional connectivity using fMRI in 38 Spanish–English bilingual (L1-Spanish) and English monolingual (L1-English) adolescents during a naturalistic science video lesson in English. Seed analyses including the left inferior frontal gyrus (pars opercularis) and posterior middle temporal gyrus showed that L1-Spanish adolescents, when learning in their second language (L2), displayed widespread bilateral functional connectivity throughout the cortex while L1-English adolescents displayed mostly left-lateralized connectivity with core language regions over the course of the science lesson. Furthermore, we identified functional seed connectivity associated with better learning outcomes for adolescents with diverse language backgrounds. Importantly, functional connectivity patterns in L1-Spanish adolescents while learning in English also correlate with their Spanish cloze reading. Findings suggest that functional networks associated with higher-order language processing and cognitive control are differentially engaged for L1 vs. L2 speakers while learning new information through spoken language.