The present study aimed to investigate the mediating role of emotion regulation and the moderating effect of rumination in the relationship between perfectionism and anxiety among university students in Mashhad. This applied research employed a descriptive–correlational design using structural equation modeling. The statistical population consisted of all university students in Mashhad, and the sample included 327 participants selected through convenience sampling. The instruments used in this study were the Multidimensional Perfectionism Scale by Flett and Hewitt, the State-Trait Anxiety Inventory by Spielberger, the Emotion Regulation Questionnaire by Gross and John, and the Ruminative Responses Scale by Nolen-Hoeksema. Data were analyzed using SPSS and Amos software. The results indicated that perfectionism directly predicted anxiety, and this relationship was mediated by emotion regulation and rumination. Moreover, rumination acted as a strengthening factor, intensifying the impact of perfectionism on anxiety. The final model demonstrated satisfactory fit indices, and both direct and indirect effects were statistically significant. These findings suggest that deficits in emotion regulation and high levels of rumination can exacerbate the link between perfectionism and anxiety. Therefore, interventions targeting anxiety in students may be more effective if they incorporate strategies to reduce repetitive negative thinking and improve emotion regulation skills.