We present results from a study aiming at investigating multimodal classroom interaction and its contribution to multilingual students’ meaning-making in science. The focus is on how science content is elaborated and negotiated through various semiotic resources. Data consist of video and audio recordings and digital photographs from three multilingual classes: a middle school physics classroom during the unit “measuring time”, a lower secondary physics classroom during the units “sound and light” and a lower secondary biology classroom during the unit “human body”. The project takes its stance in social semiotics and pragmatist theory. Data are analysed through systemic functional linguistics, multimodal analyses and Dewey’s principle of continuity. The results reveal that teachers and students were engaged in meaning-making activities involving a variety of semiotic resources with a potential to develop multilingual students’ scientific literacy. However, the teachers’ scientific starting points and perspectives on scientific literacy as well as their use of semiotic resources to some extent vary, affording different entries to science meaning-making. The study has implications for ways of promoting scientific literacy, including learning science, competent action, and communicating through different modes.