Teaching with and about technology is part of science teachers’ 21st century skills. To foster technology-enhanced practice, teachers need to acquire both technological pedagogical content knowledge (TPACK on action) and positive behavioral orientations toward technology exploitation. However, it remains unclear if the gained knowledge is applied in practice (TPACK in action). Therefore, studies are required to investigate the interplay of programs promoting TPACK on action, behavioral orientations, and resulting TPACK in action. This paper presents an approach that explicitly links pre-service science teachers’ pedagogical content knowledge (PCK) with TPACK development in two undergraduate modules, following the transformative view of TPACK. TPACK on action and behavioral orientations are captured through a questionnaire at three points in time. Additionally, lesson plans are analyzed to evaluate the quality of technology use and cognitive engagement, approximating TPACK in action. The results show a significant increase in pre-service science teachers’ (N = 133) self-rated TPACK on action and behavioral orientations between pre- and post-test, with moderate to large effects. Moreover, the analyses of lesson plans reveal a high quality of technology exploitation in the planned lessons, indicating distinctive TPACK in action after attending the modules. This theory-based approach is supported by empirical data, and highly regarded by participants, making it a successful model for course redesign at other universities.