Aim To compare: (1) self‐ and proxy‐reported quality of life (QoL) in adolescents with epilepsy, cerebral palsy (CP), both epilepsy and CP, and a representative general population sample; and (2) parental stress between parents of adolescents with epilepsy, CP, or both epilepsy and CP. Method This was a cross‐sectional observational study with 496 adolescents with epilepsy, 699 with CP, 192 with both CP and epilepsy, and 15 396 from the general population, assessed with the KIDSCREEN‐52 and Parenting Stress Index (PSI). Results All KIDSCREEN‐52 domains showed statistically significant differences across groups. The epilepsy population showed clinically better scores for ‘school environment’ than the general population (Cohen’s d=0.62). Parents scored adolescents with CP lower than adolescents with epilepsy or general populations on ‘physical health’ (d=0.57, d=0.55) and ‘social‐support and peers’ (d=0.82, d=0.91). Parents of adolescents with CP scored them lower than parents of the epilepsy group on ‘autonomy’ (d=0.62). Parents of adolescents with epilepsy scored them lower on ‘mood and emotions’ (d=0.52) and ‘social acceptance’ (d=0.66) than the general population. PSI scores were better for parents of adolescents with CP than for parents of adolescents with epilepsy (d=2.12, d=2.70, d=3.35, d=1.67). Interpretation Adolescents with epilepsy or CP self‐report equal or better QoL than the general adolescent population, which should comfort families and allow clinicians to address parental concerns. What this paper adds Adolescents with epilepsy, with or without cerebral palsy (CP), self‐reported better school environment than adolescents in the general population. Proxy quality of life (QoL) results showed clinically important differences across groups in 6 out of 10 domains of the KIDSCREEN‐52. Proxy‐reported results showed poorer QoL scores for adolescents with epilepsy or CP than the general population. Parental stress level was lower in parents of children with CP or both CP and epilepsy, than in those with only epilepsy.