Design-Based Science (DBS) is a pedagogy in which the goal of designing an artifact contextualizes all curricular activities. Design is viewed as a vehicle through which scientific knowledge and real-world problem-solving skills can be constructed. Following Anderson and Hogan's (1999) call to document the design of new science pedagogies, this goal of this article is twofold: (a) to describe DBS, and (b) to evaluate whether significant science knowledge was constructed during consecutive enactments of three DBS units. In this study, 92 students participated in the consecutive enactments of three different DBS units. The development of their scientific knowledge was assessed through posters and models constructed during the curricular enactments and by identical pre- and post-instruction written tests. The posttests showed considerable gains compared with the pretests, while the models and posters show application of this newly constructed knowledge in solving a design problem. These positive results support efforts being made to restructure school science around inquiry-based curricula in general and design-based curricula in particular. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 1081–1110, 2004