Background: Australian university students are at risk of experiencing poor mental health, being vulnerable to self‐harm and suicidal ideation. Aim: "Talk‐to‐Me" is a suicide ideation prevention Massive open online course (MOOC) previously showing it can support Western Australian university students' knowledge of identifying and responding to suicide ideation in themselves and others. Methods: A multi‐site one‐group pre‐test/post‐test design with a 12‐week follow‐up explored the efficacy of "Talk‐to‐Me" for university students Australia‐wide, evaluating the influence of COVID‐19 and location. Overall, 217 students (55% female; mage = 24.93 years [18, 60]) enrolled in this study from 2020 to 2021. Participants' responses to suicidal statements, mental health literacy, generalized self‐efficacy, help‐seeking behavior, and overall utility of the program were collected at baseline, post‐MOOC (10 weeks from baseline) and 12‐week follow‐up. The effect of time and location interaction was explored using a random‐effects regression model. Results: Findings indicated significant improvement in participants' knowledge of positive mental health support strategies (ES = 0.42, p < 0.001) and recognizing appropriate responses to suicidal statements (ES = 0.37, p < 0.001) at 10‐weeks, with further improvement at 12 weeks follow‐up (ES = 0.47 and 0.46, p < 0.001). Students reported higher generalized self‐efficacy at the 12‐week follow‐up compared to baseline (ES = 0.19, p = 0.03) and an increased tendency to seek professional help for mental health issues (ES = 0.22, p = 0.02). Conclusion: These findings provide preliminary evidence of the efficacy of the "Talk‐to‐Me" program in supporting university students across Australia to increase their suicide‐related knowledge and skills, general self‐efficacy, and overall mental fitness. [ABSTRACT FROM AUTHOR]