Background: Educational institutions worldwide have experienced the suspension of offline teaching activities in favor of online teaching due to the outbreak of the COVID-19 pandemic. However, few studies have focused on the degree of support for online learning among college students in mainland China. Therefore, the aim of this study was to investigate the degree of support for online learning among Chinese college students during the epidemic and whether depression, loneliness, family communication, and social support were associated factors. Methods: A questionnaire was used to collect cross-sectional data from 9319 college students in mainland China, and a structural equation model was analyzed. Results: The results of the study showed high degrees of support for online learning among Chinese college students during the COVID-19 pandemic, with more than half expressing support. The SEM (Structural Equation Modeling) results showed that depression had a negative and significant effect on college students’ support for online learning (β = −0.07; p < 0.001); family communication had a positive and significant effect on college students’ support for online learning (β = 0.09; p < 0.001); social support had a positive and significant effect on college students’ support for online learning (β = 0.11; p < 0.001). Conclusions: Social support and family communication can alleviate the negative psychological status of college students, and depression plays a mediating role in the effect of social support and family communication on college students’ degree of support for online learning. In addition, a significant chain-mediating effect was found of family communication, loneliness, and depression between social support and college students’ degree of support for online learning. Government and education institutions must focus on college students’ mental health issues and consider family interventions and general support that college students require.