Background: This study examined the effect of computer-supported collaborative argumentation (CSCA) on secondary school students' understanding of socio-scientific issues (SSI). Engaging students in collaborative argumentation is known to help with deepening their understanding of SSI. Methods: In this study, a mixed-method design is used to investigate 84 students' collaborative argumentation processes and outcomes. The statistical analysis, epistemic network analysis and qualitative uptake analysis results showed that CSCA was effective in supporting secondary school students' evidence-based argumentation skills on SSI. Findings and Conclusion: Several cases were presented to show how students engaged in CSCA to explore meaningful learning opportunities and how CSCA helped students' learning on SSI. Implications: The findings provided insights for future innovative teaching and learning SSI in authentic classroom settings.