To combat/control the COVID-19 pandemic, a complete lockdown was implemented in China for almost 6 months during 2020. To determine the impact of a long-term lockdown on the academic performance of first-year nursing students via mandatory online learning, and to determine the benefits of online teaching. The recruitment and academic performance of 1st-year nursing students were assessed between 2019 [prior to COVID-19, n = 195, (146 women)] and 2020 [during COVID-19, n = 180 (142 women)]. The independent sample t test or Mann-Whitney test was applied for a comparison between these two groups. There was no significant difference in student recruitment between 2019 and 2020. The overall performance of the first-year students improved in the Biochemistry, Immunopathology, Traditional Chinese Medicine Nursing and Combined Nursing courses via mandatory online teaching in 2020 compared with traditional teaching in 2019. Suspension of in-class learning but continuing education virtually online has occurred without negatively impacting academic performance, thus academic goals are more than achievable in a complete lockdown situation. This study offers firm evidence to forge a path for developments in teaching methods to better incorporate virtual learning and technology in order to adapt to fast-changing environments. However, the psychological/psychiatric and physical impact of the COVID-19 lockdown and the lack of face-to-face interaction on these students remains to be explored.