The unprecedented COVID-19 global pandemic has created many challenges across the educational domains experienced by many cultures around the world. The present study elucidates a cross-cultural comparison of college students' self-efficacy, self-regulation, and resilience between college students in the United States and China during these challenging times. A total of 479 college students from the United States and China were recruited to participate in the present study. Multivariate analyses of variance (MANOVA) were conducted, and results indicated that U.S. college students demonstrated significantly higher self-efficacy and resilience and significantly lower self-regulation than Chinese college students. Further, the implications of the present study provide suggestions for effective teaching and learning strategies that can be used to establish supportive learning environments for students from different cultural backgrounds.