The constant variation of COVID-19 has intensified the spread and recurrence of the epidemic, and education continues to be hard hit in most countries. The virtual classroom has become the main platform to replace the traditional classroom in the COVID-19 pandemic context. Due to the lack of a comprehensive understanding of college students’ perceptions of the platform system, it is essential to explore the factors and mechanisms that influence students’ willingness to use virtual classrooms consistently to improve the learning efficiency and optimize the effect of educational communication during the epidemic. This study integrates the Delone and McLean (D&M) information systems (IS) success model, expectation–confirmation model (ECM), and instructor quality factor to construct an operational model, and it used a structural equation model to analyze the 411 valid samples received from online questionnaires. The results reveal that the determinants of college students’ perceived usefulness of virtual classrooms are service quality, instructor quality, and confirmation, while system quality has no effect on perceived usefulness in the context of the COVID-19 pandemic. Secondly, system quality, service quality, and instructor quality are three critical antecedents of confirmation, and perceived usefulness and confirmation positively affect satisfaction. Finally, perceived usefulness and satisfaction directly affect college students’ continuance intention.