Background: Amid the COVID-19 pandemic, there is a need to understand caregiver preferences for their children's instructional format for the start of the 2020 to 2021 academic year. The purpose of the current study was to assess caregiver preferences for on-campus versus virtual learning at home during the fall and factors associated with these preferences. Methods: Participants were caregivers of 4436 children and adolescents who were enrolled in pre-kindergarten through high school at a large, public school district in Texas. Caregivers were asked to complete an anonymous, online survey about their initial preferences for their student's back to the school learning environment. Results: Caregivers of high- and middle-school students were more likely to endorse a preference for an on-campus/virtual hybrid instructional format and less likely to endorse a preference for a traditional, face-to-face instructional format compared to caregivers of elementary school students. Regardless of the school level, concerns about child health and safety were the factor most strongly associated with caregiver preferences for on-campus versus virtual learning at home during the fall. Conclusions: These data highlight the importance of school re-opening plans offering virtual options and addressing caregiver concerns about children's health and safety amid the COVID-19 pandemic.