This dissertation investigated the impact of prior knowledge, course design, and technology preparation on pre-service teachers' development of technological pedagogical content knowledge (TPACK) in a teacher education program at a large Midwestern land-grant university over a span of nine academic years (Mishra & Koehler, 2006). In this study, 1,246 pre-service teachers participated by responding to both pre- and post-TPACK surveys. A series of statistical analyses were used to analyze the quantitative data collected from these pre- and post-surveys. First, descriptive analyses and a two-step cluster analysis were used to group pre-service teachers into different clusters based on their pre-TPACK scores (low and high). A two-group model was found to be the best fit, and thus, pre-service teachers were grouped into these two clusters. Cluster 1 pre-service teachers reported lower pre-TPACK scores compared to cluster 2 pre-service teachers. Paired-sample t-tests were run to examine whether there were differences in the post-TPACK and TPACK-development scores. The results revealed that cluster 2 pre-service teachers reported higher post-TPACK scores, while cluster 1 pre-service teachers had higher TPACK-development scores. Second, two-way MANOVA tests were used to investigate the impact of prior knowledge, course design, and technology preparation on pre-service teachers' post-TPACK and TPACK-development scores. All three variables were found to be statistically significant factors. In particular, a content-specific TPACK course design was more effective than the general course design. Cluster 2 pre-service teachers who reported higher pre-TPACK scores still had higher post-TPACK scores. Conceptual and practical implications are discussed. Future research directions are offered.