Project-based learning (PjBL) allows nursing students to participate in real problem-solving, construct knowledge, and improve their nursing skills in the process of accomplishing meaningful projects. This study was conducted to develop a PjBL program on high-risk newborn care for nursing students and evaluate its effects. A quasi-experimental study using a nonequivalent control group pretest–posttest design was employed between June and December 2021. The participants were 45 nursing students (24 in the experimental group and 21 in the control group). A PjBL program involving the creation of an educational video clip about high-risk newborn care for nursing students was developed, and the experimental group took part in PjBL. The participants’ nursing competency for high-risk newborns, self-leadership, and practicum-related stress were assessed. In the experimental group, nursing competency for high-risk newborns increased and practicum-related stress decreased to a greater extent than in the control group. However, the change in self-leadership was not significantly different between the experimental and control groups. PjBL effectively improved students’ nursing competency for high-risk newborns and decreased their practicum-related stress. PjBL will be utilized to enhance nursing students’ expertise in high-risk newborn care.