Online learning requires higher levels of self-regulation in order to achieve optimal learning outcomes. As nursing education moves further into the blended and online learning venue, new teaching/learning strategies will be required to develop and enhance self-regulated learning skills in nursing students. The purpose of this study was to compare the effectiveness of team-based learning (TBL) with traditional instructor-led (IL) learning, on self-regulated online learning outcomes, in a blended undergraduate research and evidence-based practice course. The nonrandomized sample consisted of 98 students enrolled in the IL control group and 86 students enrolled in the TBL intervention group. The percentage of total possible online viewing time was used as the measure of self-regulated online learning activity. The TBL group demonstrated a significantly higher percentage (p < 0.001) of self-regulated learning activities than the IL control group. The TBL group scored significantly higher on the course examinations (p = 0.003). The findings indicate that TBL is an effective instructional strategy that can be used to achieve the essential outcomes of baccalaureate nursing education by increasing self-regulated learning capabilities in nursing students.