Background. Work engagement and patient-safety outcomes in nursing practice are critically significant. However, most previous studies evaluating antecedents of work engagement and patient-safety outcomes have used cross-sectional designs. Aims. To investigate the effects of job resources (organizational support and leader empowerment) and core self-evaluation on nurses’ work engagement and patient-safety outcomes. Methods. This longitudinal study surveyed 2,618 registered nurses from 17 public hospitals in XuZhou, China. Participants completed self-report questionnaires on organizational support, leader empowerment, and core self-evaluation at baseline. Work engagement and patient-safety outcomes were collected 18 months after the baseline. The mixed linear regression and Johnson–Neyman statistical analysis were used to analyze data. Results. Organizational support was an outsize predictor of nurses’ work engagement, followed by core self-evaluation and leader empowerment. Organizational support and core self-evaluation were equally crucial for predicting patient-safety outcomes. Moreover, the positive impact of leader empowerment on patient-safety outcomes became significant when the core self-evaluation score was below 51. Conclusions. This study demonstrated that organizational support, leader empowerment, and core self-evaluation are important determinants of nurses’ work engagement and patient-safety outcomes. Implications for Nursing Management. Hospital managers and nurse leaders should consider providing multiple supports to motivate staff nurses to engage in work. When nurses’ core self-evaluation is low, empowering training for nurse leaders should be essential to reduce adverse patient events.