Background: The growing population of students that are learning science through a Content and Language Integrated Learning approach (CLIL) has led to concerns about these students’ ability to fully participate in a rich classroom discourse to develop content knowledge. A lack of information about science development through classroom discourse in CLIL settings brought us to focus on the questions teachers ask in upper secondary CLIL biology classrooms. Our aim was to understand how these questions effect science content learning opportunities. A multiple-case study design was implemented to examine and understand the complexities of teacher-student interactions. Data were collected in three case studies, each located in a different school (two in Germany and one in Italy), where CLIL senior secondary science classrooms were observed and audio-recorded. Classroom talk transcripts were analyzed using a mixed methods approach to discourse analysis. Results: Findings suggest that a teacher’s strategic use of questions has the potential to promote both science understanding and science language development. Questioning contingent on students’ answers was observed to both promote content understanding and to lessen the linguistic demand on CLIL students by splitting both reasoning processes and language production into more manageable units. In addition, a higher level of cognitive engagement was present only when students managed to participate in the classroom discourse with answers longer than single utterances. To allow students to actively participate in the classroom discourse, teachers were observed adopting and promoting translanguaging practices, that is, the flexible use of more than one linguistic code. Furthermore, teachers asked language-related questions that promoted both understanding and use of disciplinary language. Conclusions: The questioning practices observed in this study offer both practitioners and researchers ways of understanding issues of content access in upper secondary CLIL science classrooms. We recommend STEM teachers in CLIL settings not to oversimplify the linguistic demand on students, as this leads to an oversimplification of content. To lessen the linguistic barriers, practical strategies are recommended to support both cognitively and linguistically productive questioning in STEM CLIL classrooms.