This study examined the relationship between teacher efficacy and professional development among in-service K-12 teachers. A content-rich teacher professional development program was analyzed over the course of two years using a sequential explanatory mixed-methods approach. First, in the quantitative phase (QuantP1), a total of 138 teachers were assessed using the Teacher Sense of Efficacy Scale (TSES) before and after a three-month intervention aimed at teacher intellectual growth and confidence gain. Second, in the first qualitative phase (QualP1), open-ended responses from 180 teachers on four anonymous questions were coded and categorized. Third, in the second qualitative phase (QualP2), eight teacher participants’ interviews were recorded, transcribed, and analyzed to provide insights into the experiences of participating in the professional development intervention. Results from the quantitative phase of the study indicated statistically significant gains after the intervention on teacher efficacy with small to moderate effect sizes. These statistically significant main effect differences on time were found overall and on three subscales of the TSES, and on overall efficacy and on student engagement subscale when looking at the interaction of time and years of teaching experience. Results from the qualitative phase of the study indicated that teacher participants valued (1) relevant learning experiences related to content research, (2) time to interact with other K-12 teachers, and (3) support from content-expert professors. These findings relate to existing research on effective teacher professional development aimed at the importance of content knowledge, collaboration among colleagues, and expert coaching. Implications for increasing teacher efficacy through professional development include supporting relevant research activities for teachers (cognitive mastery experiences), promoting varied interactions among K-12 teacher colleagues (vicarious experiences), and encouraging constructive, positive feedback from credible experts (verbal persuasion).