Background The nursing profession requires ethical and legal regulations to guide nurses’ performance. Ethical climate plays a part in shaping nurses’ ethical practice. Therefore, ethico-legal aspects and ethical climate contribute to improving nurses’ ethical practice and competencies with reducing medical errors in hospital settings. Objective This study examined the effect of ethico-legal aspects and ethical climate on managing safe patient care and medical errors among nurses. Materials and methods A cross-sectional correlational study was carried out on 548 nurses. Data were collected through self-administered questionnaires about nurses’ knowledge in both ethical and legal aspects, ethical practice, competencies, ethical climate and experience with medical error. Results The main sources of nurses’ knowledge of ethical and legal aspects were undergraduate lectures, job experience and colleagues. Nurses’ knowledge in both ethical and legal aspects, nurses’ ethical practice and competencies were insufficient. Nurses fairly perceived their ethical climate. Also, nurses experienced medical errors about 22.6% in their units. Nurses’ knowledge of ethical and legal aspects, as well as the ethical climate were positive predictors of inadequate nurses’ ethical practice and competencies. Additionally, nurses’ knowledge in both ethical and legal aspects, ethical climate and practice had a negative influence on the occurrence of medical errors. Conclusion Enhancing nurses’ knowledge in both ethical and legal aspects as well as ethical climate could significantly influence improving nurses’ ethical practice, competencies and reducing medical errors in the study units. Therefore, planning for enhancing the nurses’ ethico-legal learning and ethical climate seems to be mandatory.