The relationship between mental health problems, Autism Spectrum Disorder (ASD) and challenging behaviour among children and adolescents is complex and multifaceted. The study investigated practitioners' perception of comorbidity of mental health and ASD in the management of challenging behaviours among children and adolescents in Kenya. Target population was 3490 practitioners. Sample size was 1047, comprising of 38 assessment staff, 27 mental health workers 548 regular teachers, 294 teachers from special schools, and 140 teachers from special units for children with ASD. Stratified and purposive sampling techniques were used. Interviews and structured questionnaires were used. Test-retest yielded a coefficient of 0.78 while Cronbachs' reliability coefficient was 0.830. There was a positive significant correlation between perception of challenging behaviours and mental health problems (r = 0.415, p = 0.000). Challenging behaviour perceptions have a negative significant effect on behaviour management strategies, ([beta] = -0.163, p = 0.000) implying that the choice of management strategies is dependent on the perceptions. Challenging behaviours accounts for 2.7% variance in the choice of the management strategies, R[superscript 2] = 0.027, F(1,1045) = 28.471, p = 0.000.The practitioners' perception of mental health and comorbid ASD, showed that children with ASD, when enduring life stressors, can be at a higher risk of mental health difficulties than their peers There is need for multidisciplinary synergy in developing effective challenging behaviour programmes for children and adolescents with ASD.