Autistic young people experience high levels of co-occurring mental health difficulties, including anxiety, depression and behavioural difficulties, across their lifespan. Understanding the neuropsychological mechanisms which underlie these difficulties is vital in developing personalised supports and interventions. Cognitive inflexibility is one candidate mechanism which is associated with co-occurring mental health comorbidities but is also associated with other features of autism such as restricted and repetitive behaviours. This study investigates the distinct longitudinal association between cognitive inflexibility, measured using objective neuropsychological measures and emotional and behavioural problems across adolescence and early adulthood. Eighty-one autistic people from a population-based longitudinal study were assessed at 16 and 23 years on measures of emotional and behavioural problems, with cognitive inflexibility, restricted and repetitive behaviours and verbal intelligence quotient measured at 16 years. We used structural equation modelling to investigate the relationship between cognitive inflexibility and emotional and behavioural symptoms at both timepoints while accounting for the severity of restricted and repetitive behaviours and verbal intelligence quotient. Our results indicate an effect of cognitive inflexibility on increased behavioural problems at 16 years and emotional problems across timepoints, which is distinct from restricted and repetitive behaviours and verbal intelligence quotient. Exploratory mediation analyses suggest that cognitive inflexibility may be one mechanism through which emotional difficulties are maintained longitudinally.