Remote work in pandemic times has become a strategic alternative for organizations and has persisted in the post-pandemic context, remaining present in hybrid models of work arrangements, blending in-person work and telework. Thus, this paper proposes a model to identify the relationships between leadership, human resource management (HRM) practices, and quality of life in teleworking (QoLT) for civil servants. For this purpose, a structural model was tested in which HRM practices mediated the relationship between leadership and QoLT. The relationships assumed in the analysis of the tested mediation model were significant, confirming all four hypotheses researched. The novelty of the tested mediation model is the greatest contribution of this work, demonstrating the crucial role that HRM practices play in the relationship between leadership and QoLT. As practical implications, this research has yielded a diagnosis, allowing for a better understanding for public managers of how leadership and HRM practices are related and how they influence quality of life in the challenging context of teleworking. The findings suggest that leadership has a strong impact on HRM practices, highlighting the crucial role of leadership in shaping teleworkers’ perceptions of HRM practices. Additionally, leadership significantly influences the quality of life in telework, amplifying this impact through the perception of HRM practices. Therefore, leaders should be attentive to how relationship-building, training and development, and performance and competency evaluation in HRM practices are implemented and executed, as they profoundly influence the promotion of quality of life, considering the complex and challenging environment of telework, including workload, social distance, and work–family conflict.