Visuo-semiotic models, such as Lewis structures and ball & stick models, are widely used to enhance students' learning. However, there is limited research about the impact of these models on specific visuo-semiotic reasoning skills. In the current research, we aimed to determine the extent to which physical molecular models could enhance specific visuo-semiotic reasoning skills among students. The research question that we explored was, "what is the impact of physical molecular models on Grade 11 students' visuo-semiotic reasoning skills related to Lewis structures and ball & stick models of ammonia?" In this mixed-methods research, we collected data from purposively selected Grade 11 chemistry students aged between 15 and 18 from an under-resourced school in South Africa. Through a quasi-experimental design, participants in the experimental group (n = 101) used physical molecular models to learn about Lewis structure and ball & stick models of ammonia while participants in the control group (n = 100) did not. We subsequently tested students' visuo-semiotic reasoning skills. Results show that using physical molecular models significantly improved students' visuo-semiotic reasoning skills and reduced associated learning difficulties. We, therefore, recommend that these models should be used as an instructional tool to enhance learning.