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Strategies are an important component of self-regulated learning frameworks. However, the characterization of strategies in these frameworks is often incomplete: (1) they lack an operational definition of strategies; (2) there is limited understanding of how students develop and apply strategies; and (3) there is a dearth of systematic and generalizable approaches to measure and evaluate strategies when students’ work in open-ended learning environments (OELEs). This paper develops systematic methods for detecting, interpreting, and analyzing students’ use of strategies in OELEs, and demonstrates how students’ strategies evolve across tasks. We apply this framework in the context of tasks that students perform as they learn science topics by building conceptual and computational models in an OELE. Data from a classroom study, where sixth-grade students (N = 52) worked on science model-building activities in our Computational Thinking using Simulation and Modeling (CTSiM) environment demonstrates how we interpret students’ strategy use, and how strategy use relates to their learning performance. We also demonstrate how students’ strategies evolve as they work on multiple model-building tasks. The results demonstrate the effectiveness of our strategy framework in analyzing students’ behaviors and performance in CTSiM.