Research into early screen exposure has raised growing concerns about its impact upon children’s neuropsychological well-being. However, possible pathways remain unclear. This study therefore aimed not only to evaluate the association between screen exposure during the ages of 0–3 years and preschoolers’ autistic-like behaviors, but also the mediating roles of the frequency of caregiver-child interaction, sleep duration and level of participation in outdoor activities. Based on the 2017 survey of the Longhua Child Cohort Study, data of 29,595 child-caregiver dyads were obtained via a caregiver-reported questionnaire, with the data from 29,461 dyads included in the data analysis. Multiple linear and logistic regression models were employed to estimate the associations between screen exposure, caregiver-child interaction, sleep duration, outdoor activities, and children’s autistic-like behaviors. The results indicated that screen exposure during 0–3 years of age was associated with the presence of autistic-like behaviors at preschool age, and the strength of the association was enhanced with the increase of average daily screen time (Odds Ratios (ORs) ranging from 1.358 to 4.026). The frequency of caregiver-child interaction and sleep duration mediated 5.32% and 1.19% of the variance of the association respectively, but outdoor activities did not mediate the association. Our findings indicate that preschoolers who are exposed to screens at aged 0–3 years might have an increased risk of autistic-like behaviors, and that, the frequency of caregiver-child interaction and sleep duration might function as potential mediators of this association.