Autism spectrum disorder (ASD) is a complex, multifaceted, developmental brain disorder that is based on behavioral criteria and is increasing in frequency. Despite decades of research, reliable biomarkers and effective therapeutic approaches remain elusive. Here we provide a focused review of research literature that suggests an involvement of the neurotransmitter serotonin (5-HT) in the etiology of the disorder. We describe the role that 5-HT plays in the maturation of brain structure and function as relevant to the neuropathologies of ASD. We discuss the role of 5-HT in autoimmune disorders, inflammation, and the gut–brain axis, all of which have been associated with ASD and are identified as risk factors for maternal transmission. Our review supports the hypothesis that the interplay of peripheral and central 5-HT levels in the mother and offspring, and placental 5-HT synthesis impacts early brain development in genetically vulnerable individuals and result in the neuropathologies associated with ASD.