This three-paper dissertation explores sensemaking in undergraduate science classrooms. The first two studies explore the sensemaking of mathematical equations in science and the third study investigates students’ sensemaking of one scientific phenomenon. Together, these studies provide new resources for research and contribute to theory on the sensemaking of mathematical equations and scientific phenomena. In the first study, an extensive and systematic literature review was performed to identify possible types of sensemaking for mathematical equations in science. Relevant publications around sensemaking in both the science education and mathematics education literature were reviewed. The resulting Sci-Math Sensemaking Framework includes nine categories for different types of sensemaking, five in the mathematics dimension and four in the science dimension. This novel framework provides researchers with an analytical tool to explore sensemaking in the instruction of mathematical equations across the scientific disciplines. In the second study, the Sci-Math Sensemaking framework was used to understand the sensemaking opportunities provided by four undergraduate biology instructors teaching mathematical equations in the context of population growth. A multiple-case study was conducted with each instructor’s lesson(s) described and the different sensemaking opportunities identified. A comparison across instructors revealed that instructors provided different types of mathematics sensemaking and science sensemaking in their class, and they organized these different types of sensemaking opportunities in different ways. Instructors combined sensemaking across categories in the Sci-Math Sensemaking Framework in three different ways, two of which had not been previously identified in the literature. The third study investigated undergraduate biology students’ sensemaking of the scientific phenomenon of mutation. A qualitative analysis was performed on students’ written responses to open-ended questions on how mutations arise in animal populations. Although the questions should have elicited an explanation involving a biological process, many students responded with only a definition of mutation. It is suggested that instructional approaches should place greater emphasis on understanding the process-related features of mutation.