Students tend to think of their science courses as isolated and unrelated to each other, making it difficult for them to see connections across disciplines. In addition, many existing science assessments target rote memorization and algorithmic problem‐solving skills. Here, we describe the development, implementation, and evaluation of an activity aimed to help students integrate knowledge across introductory chemistry and biology courses. The activity design and evaluation of students' responses were guided by the Framework for K‐12 Science Education as the understanding of core ideas and crosscutting concepts and the development of scientific practices are essential for students at all levels. In this activity, students are asked to use their understanding of noncovalent interactions to explain (a) why the boiling point differs for two pure substances (chemistry phenomenon) and (b) why temperature and base pair composition affects the stability of DNA (biological phenomenon). The activity was implemented at two different institutions (N = 441) in both introductory chemistry and biology courses. Students' overall performance suggests that they can provide sophisticated responses that incorporate their understanding of noncovalent interactions and energy to explain the chemistry phenomenon, but have difficulties integrating the same knowledge to explain the biological phenomenon. Our findings reinforce the notion that students should be provided with opportunities in the classroom to purposefully practice and support the use and integration of knowledge from multiple disciplines. Students' evaluations of the activity indicated that they found it to be interesting and helpful for making connections across disciplines.