Autism spectrum disorders (ASD) have long-term implications on functioning at multiple levels. In this perspective, we offer a brainstem-informed autism framework (BIAF) that traces the protracted neurobehavioral manifestations of ASD to early life brainstem dysfunctions. Early life brainstem-mediated markers involving functions of autonomic/arousal regulation, sleep-wake homeostasis, and sensorimotor integration are delineated. Their possible contributions to the early identification of susceptible infants are discussed. We suggest that the BIAF expands our multidimensional understanding of ASD by focusing on the early involvement of brainstem systems. Importantly, we propose an integrated BIAF screener that brings about the prospect of a sensitive and reliable early life diagnostic scheme for weighing the risk for ASD. The BIAF screener could provide clinicians substantial gains in the future and may carve customized interventions long before the current DSM ASD phenotype is manifested using dyadic co-regulation of brainstem-informed autism markers.