Non-suicidal self-injury is commonly explained using an emotion regulation framework. Increasingly, early maladaptive schemas (EMS) are also used to conceptualise self-injury. However, there is an absence of research examining the relationship between EMS, emotion regulation, and self-injury. The current study attempted to address this gap by comparing youth with and without a history of self-injury on measures of emotion regulation difficulties and EMS, specifically Abandonment/Instability and Defectiveness/Shame. Specifically, we were interested in assessing whether difficulties in emotion regulation mediated the relationship between EMS and self-injury. Four hundred and three Australian secondary and university students aged between 16 and 25 years, completed measures of self-injury, EMS, and difficulties in emotion regulation. We found significant and positive relationships between Abandonment/Instability, Defectiveness/Shame and six emotion regulation difficulties. Young people with a self-injury history reported more difficulties in emotion regulation compared to those who had never self-injured. For each of the EMS, there was a direct effect on self-injury status, as well as an indirect effect via total emotion regulation difficulties. There was a significant indirect effect of Abandonment/Instability on self-injury via limited access to emotion regulation strategies. Results contribute to our understanding of mechanisms underlying the association between EMS and self-injury, that is, through emotion regulation difficulties. Results are discussed with reference to clinical implications, suggesting that targeting both EMS and emotion regulation difficulties may be appropriate when working with young self-injurers.