Moral distress in and ethical climate of health care institutions are highly intertwined subjects and have been linked to various quality of care indicators as well as job turnover intentions among health care professionals. Predominantly, both phenomena have been studied in intensive care, palliative and in-hospital settings. We aimed to explore the experience of moral distress by general practitioners (GPs), the role of ethical climate in GP moral distress and how ethical climate and moral distress can result in moral resilience in general practice. Between April and October 2021, we interviewed 13 doctors active in general practice in Flanders, Belgium, through semi-structured interviews. Data were processed and analysed using the Qualitative Analysis Guide of Leuven (QUAGOL). Most GPs had ample experience with morally distressing situations. Causes, determinants, and consequences do not differ significantly from other care settings. Moral distress can arise from conflicting views of good care, communication problems, and impending harm to third parties. We detected determinants of moral distress on micro-, meso- and macrolevels. GPs associate moral distress with job turnover and emotional, physical, existential, and quality of care effects. Several malleable factors can contribute to resilient ethical climates. This requires acquisition of vocabulary, skills, and knowledge. Moral distress and ethical climate are important emerging themes for GPs. This research identifies determinants and effects of moral distress and ethical climate in primary care and could help GPs leverage moral distress experiences into morally resilient primary care through multiple suggested strategies.