Mental health literacy (MHL) training is essential in college environments. These programs are commonly delivered in-person via workshops or for-credit courses. Campuses now seek high-quality online options. We compare the effectiveness of a for-credit MHL course against a comparison course, focusing on whether online asynchronous delivery was as effective as in-person synchronous delivery. This quasi-experimental pretest/posttest treatment/comparison study included 1049 participants across five semesters (pre-COVID-19) who were 18 years or older and self-selected enrollment in a Mental Health Awareness and Advocacy (MHAA) course (treatment; n = 474) or a general lifespan development course (comparison; n = 575). Using linear mixed effect modeling, changes in MHL were compared across groups and across online/in-person modalities. Students in the treatment group significantly increased their MHL knowledge ([beta][subscript Identifying] = 0.49, p < 0.001; [beta][subscript Locating] = 0.32, p < 0.001; [beta][subscript Responding] = 0.46, p < 0.001) and self-efficacy ([beta] = 0.27, p < 0.001), and treatment effects did not differ across modalities. With increased concern regarding mental health issues of isolated college students during the COVID-19 pandemic, this study supports the efficacy of delivering MHL courses online.