The number of technological pedagogical and content knowledge (TPACK) studies has been increasing day by day; however, limited number of studies has provided both quantitative and qualitative findings based on teachers' learning by design experiences. This study aimed to reveal the changes in pre-service teachers' TPACK competencies in the educational website design process and their experiences in the design process within the scope of a course based on TPACK framework and the learning by design approach. Designed as an embedded mixed design research, the study was conducted with 28 pre-service teachers. The data were collected through the TPACK-deep scale, a survey and e-mails sent to the instructors. The research concluded that the learning by design approach brings pre-service teachers' TPACK competencies in highly effective significant contributions. Moreover, it was revealed that the design process expands pre-service teachers' schemas regarding the properties which digital instructional materials should possess. The research also enlightened the motivating factors such as receiving support and the challenging factors such not being able to use software for the pre-service teachers in the design process. Finally, the findings were interpreted within the framework of TPACK and the learning by design approach and recommendations were made for future practices and studies.