Teacher well-being, which includes emotional, physical, and mental health, is vital for enhancing teacher efficacy and improving educational outcomes. The purpose of the study was to examine the interplay between motivation and well-being, focusing on how these factors affect teacher performance and retention in Ghana. To achieve this purpose, the study adopted a quantitative research approach underpinned by a descriptive research design. The target population comprised 40,000 senior high school teachers from five regions in Ghana. About 485 teachers were sampled using simple random selection and proportionate stratified sampling. This study examines the interplay between motivation and well-being, focusing on how these factors affect teacher performance and retention. By utilizing the PERMA model and emphasizing intrinsic and extrinsic motivators, the research offers practical recommendations tailored to the Ghanaian educationalGhanaian education context. Data were gathered using modified versions of the Teacher Well-Being Scale, Work Task Motivation Scale, and Teaching Satisfaction Scale. Multiple linear regression and analysis of variance (ANOVA) were used to analyze research questions 1 and 2, respectively. The results showed that strong relationships, meaningful involvement, and happy emotions were significant predictors of the development of supportive settings for Ghanaian teachers. The study’s findings, reducing burnout, increasing retention, and eventually attaining high-quality education in Ghana, all depend on improving teacher welfare through focused interventions.