The contributions of computer self-efficacy (CSE) to university students’ learning anxiety (LA) in online classes (OCs) has largely remained unexplored in the higher education context of Iran. Thus, this mixed-methods study aims to inspect the correlation between Iranian university students’ CSE and LA from both quantitative and qualitative perspectives. For this purpose, a total of 290 undergraduate students, including male students (n = 64) and female students (n = 226) for the quantitative part and a sample of 18 undergraduate students, consisting of male students (n = 7) and female students (n = 11) for the qualitative part were chosen through a random sampling method at Ayatollah Borujerdi University, Iran. The participants were asked to fill out a Computer Self-Efficacy Questionnaire, an Anxiety in Online Classes Questionnaire, and a reflective written statement. The collected data were analyzed using a Pearson correlation coefficient test, a multiple regression analysis test, and a thematic coding approach. Findings documented that the participants’ CSE and LA were negatively correlated in OCs. Additionally, the results indicated that the participants’ LA was mainly affected by advanced and beginning factors of CSE. Furthermore, the qualitative findings yielded five overarching themes, including ‘high CSE leads to more risk-taking’, ‘high CSE leads to increased motivation’, ‘high CSE leads to useful experiences’, ‘high CSE leads to accessing additional knowledge sources’, and ‘high CSE leads to increased self-regulation’. The study concludes by offering some implications for pertinent stakeholders.