This paper builds on the current literature base about learning progressions in science to address the question, “What is the nature of the learning progression in the content domain of the structure of matter?” We introduce a learning progression in response to that question and illustrate a methodology, the Construct Modeling (Wilson, ) approach, for investigating the progression through a developmentally based iterative process. This study puts forth a progression of how students understand the structure of matter by empirically inter‐relating constructs of different levels of sophistication using a sample of 1,087 middle grade students from a large diverse public school district in the western part of the United States. The study also shows that student thinking can be more complex than hypothesized as in the case of our discovery of a substructure of understanding in a single construct within the larger progression. Data were analyzed using a multidimensional Rasch model. Implications for teaching and learning are discussed—we suggest that the teacher's choice of instructional approach needs to be fashioned in terms of a model, grounded in evidence, of the paths through which learning might best proceed, working toward the desired targets by a pedagogy which also cultivates students’ development as effective learners. This research sheds light on the need for assessment methods to be used as guides for formative work and as tools to ensure the learning goals have been achieved at the end of the learning period. The development and investigation of a learning progression of how students understand the structure of matter using the Construct Modeling approach makes an important contribution to the research on learning progressions and serves as a guide to the planning and implementation in the teaching of this topic. © 2017 Wiley Periodicals, Inc. J Res Sci Teach 9999:1024–1048, 2017