In the United States, teachers' job-related stress and self-efficacy levels across all grades are influenced in some manner by the demands of high-stakes testing. This sequential mixed-methods study aimed at examining the dynamics among assigned subject matter, teacher job-related stress, and teacher self-efficacy in a large south-eastern Texas school district. Quantitative data were collected via the "High Stakes Testing on Self-Efficacy and Teacher Stress Survey" from a convenience sample of 145 teachers, while qualitative data were gathered during focus-group sessions at the elementary, middle and high school levels. Findings indicated that assigned subject matter did not influence teacher self-efficacy, but did influence teachers' job-related stress. Additionally, a relationship was found to exist between teacher job-related stress and teacher self-efficacy. Teachers reported lack of time, modifications to curriculum, and testing of special education populations as contributions to their job-related stress, and school leadership and educational triage as impacting their teacher self-efficacy.