We investigate in-service teachers’ scientific engagement in a blended online science inquiry course. We analyze a shift from teachers following instructions to doing science themselves, and we characterize it at two levels: first, in how teachers engaged in individual sense-making; and second, in how they oriented to the online community as a space for collaboration and collective knowledge building. This progress, we show, was made possible by a shift in how the teachers framed the course—how they understood and interpreted the purpose of the activities—a shift that entailed both epistemological and affective dynamics. This shift in framing was supported by the instructors’ efforts to attend to and address participants’ epistemology and affect, both in face-to-face and in online interactions. A key implication of this study is the importance of instructional attention to epistemology and affect to create online learning environments that promote productive framings of scientific inquiry.