Objective This cross-sectional study investigated the knowledge, attitudes, and practices (KAP) of Vietnamese university students regarding COVID-19. Methods A validated questionnaire (Cronbach's alpha = 0.71) was used to survey 1,025 students. A convenience sampling method was used for recruiting students from April to May 2022. The Wilcoxon rank-sum test and the Kruskal–Wallis rank-sum test/Dunn test for multiple comparisons were employed to compare students' KAP scores between two groups and among three groups or more, respectively. Factors associated with students' COVID-19 KAP scores were determined via univariate and multivariate linear regression models. Variables in the multivariate linear regression models were chosen using the Bayesian Model Averaging method in R software version 4.2.0. Results A majority of students had good knowledge (75.61%), positive attitudes (98.24%), and good practices toward COVID-19 (94.93%). Regarding the COVID-19 knowledge, the proportions of students who knew that mosquito bites and exposure to/eating wild animals would not lead to COVID-19 infection were not high (47.22 and 34.34%, respectively). More importantly, 70.34% of students thought that vitamins and minerals could help prevent or cure COVID-19. Antibiotics were the first choice for COVID-19 treatment of 438 students (42.73%). Nearly half of students (48.0%) bought antibiotics to keep at home in case of COVID-19 infection. The average KAP scores of medical students (19.97 ± 3.99, 45.10 ± 3.94, 9.72 ± 1.78) and females (18.67 ± 4.44, 44.79 ± 3.79, 9.36 ± 1.84) were significantly higher than those of non-medical students (16.48 ± 4.37, 43.33 ± 4.03, 8.68 ± 1.87) and males (17.01 ± 4.55, 42.79 ± 4.39, 8.77 ± 1.97), respectively (p < 0.001). Older students were more likely to have good knowledge and practices than the younger ones (p < 0.001). In addition, students using websites of the World Health Organization/the Ministry of Health and scientific articles to seek COVID-19 information were significantly associated with higher KAP scores when compared with those not using these sources (p < 0.001, p < 0.001, and p = 0.00139, respectively). Conclusion Students' KAP scores significantly varied by age, sex, major, and sources of COVID-19 information. Although many students had sufficient knowledge, positive attitudes, and good preventive practices toward COVID-19, additional education and training strategies are paramount, especially for non-medical students and males.