This explanatory sequential mixed-methods study examined the prevalence of work-related burnout among academic librarians in the southeastern United States, focusing on its relationship with demographics, perceived leadership practices, and turnover intention. The study also aimed to understand how leadership practices influence work-related burnout in this population. Data were collected in two phases from a sample of 512 academic librarians. Phase I (quantitative) utilized the Copenhagen Burnout Inventory’s work-related subscale and the Leadership Practices Inventory: Observer, while Phase II (qualitative) included two open-ended questions from an online survey and 17 semi-structured interviews. Quantitative results revealed significant differences in work-related burnout based on age, years in position, and turnover intentions, with no effects for sex or race. A significant relationship was found between leadership practices and burnout, with leadership practices explaining approximately 15% of the variance as indicated by an R2 value of 0.151. Qualitative findings highlighted two leadership practices, Enable Others to Act and Model the Way, as having the most impact on work-related burnout, although external factors (e.g., work overload, staffing) were also identified as significant. Nearly half of the academic librarians were considering leaving their positions due to work-related burnout. This study offers valuable insights for academic library leadership, professional organizations, and institutional administration by providing evidence-based intervention strategies. It uniquely contributes to the professional literature by using instruments not widely used in the academic library context. The findings offer important implications for further research and practical applications in the academic library context. To reduce work-related burnout, leaders should serve as role models and focus on empowering academic librarians to reduce work-related burnout, cultivate a supportive work environment, and improve librarian retention.