Concerns about student persistence in online college courses have increased since the onset of the COVID-19 pandemic. This study examined factors associated with self-selection into asynchronous versus synchronous online course sections and effects of course format, self-efficacy, and self-regulatory behaviors on course withdrawal rates and final grades in Introductory Psychology. We assessed learning outcomes of students (N = 563, Mean age = 20.3 years) enrolled in Introductory Psychology at a nonselective, minority-serving institution in Spring 2021. Half of the sections were fully asynchronous; half met synchronously via Zoom. Students enrolled in asynchronous sections were more often first semester students; asynchronous students were less likely to access the online textbook or check Blackboard settings before submitting their first assignment. While students enrolled in synchronous sections more often reported challenges sustaining attention and motivation, students enrolled in asynchronous sections more often reported difficulties managing coursework and work obligations. Controlling for demographic factors, students in asynchronous sections had a higher risk of withdrawing, as did students with lower self-efficacy and those reporting family obligations. For students completing the course, final grades were associated with accessing the textbook, reading comprehension, and demographics, but not with course format or self-efficacy. These findings provide insight into factors that predict enrollment in online course formats and subsequent associations with learning outcomes.