Emotion regulation has been suggested as a pathway through which personality traits (e.g., extraversion or neuroticism) affect psychological well-being. However, the pathway needs further investigation across cultures due to variations in parts of the relationship reported in recent culture research. With an aim of improving current understanding of the pathway, we investigated the role of emotion regulation mediating the link between personality traits and well-being across two college samples from different cultural backgrounds: Korea and the United States (US). Results of mediation analysis revealed that the extraversion-well-being relationship was fully mediated by the degree to which individuals regulate negative emotions in both Korean and US samples. However, the neuroticism-well-being relationship was partially mediated by emotion regulation in the US sample, while it was fully mediated in the Korean sample. The role of emotion regulation differently functioning across cultures suggests the importance of investigating cultural-specific mechanism of psychological processes.