Autism spectrum disorder (ASD) is a serious childhood-onset disorder with a significant impairment in social and language development. Behavioral symptoms including aggression and self-injury are common among this population. The only second-generation antipsychotic drugs, which are proved to be effective in the treatment of disruptive behaviors in children and adolescents with ASD are risperidone and aripiprazole. Clozapine had little attention although its high anti-aggressive effect in autism has been showed by open-label reports. Here we present a case with ASD and severe disruptive behaviors and successful treatment of disruptive behaviors with clozapine. X was a 10 years old boy when he was first admitted to our outpatient clinic with complaints of aggressive outbursts destroying household objects and harming his mother. He was diagnosed with autism at the age of three. At the time of the referral he had few meaningful words, he was screaming constantly and doing some stereotypic movements. He was not responding his name or initiating any social contact. He also had obsessive-compulsive symptoms. For the last three years, he has received mirtazapine, şuoxetine, sodium valproate, quetiapine, olanzapine, aripiprazole, risperidone, haloperidol, chlorpromazine, clonazepam, either alone or in combination, for his aggressive behaviors with no significant effect. He was hospitalized for severe disruptive behaviors and after getting his legal guardian’s consent he was started on clozapine and the dose was gradually increased to 300 mg daily and 500 mg/day sodium valproate was added for potential seizures. His aggressiveness and disruptive behaviors markedly improved within two weeks after the target dose for clozapine (300 mg/day) was reached. His global improvement rating on Clinical Global Impression–Improvement Scale (CGI-I)was 2 (much improved). His aggressive outbursts remained decreased for the following six months. Clozapine was well tolerated by the patient except slight increase in obsessive-compulsive features. Clozapine can be well tolerated by adolescents with ASD and it may help improving severe disruptive behaviors not responding first-line antipsychotics. There is a need for further research on the effectiveness and safety of clozapine in the treatment of children and adolescents with ASD accompanied by disruptive behaviors.