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Objective: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). Data Sources: We searched PubMed and Embase databases for relevant studies from inception to August 2022. Study Selection and Data Extraction: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle–Ottawa Scale. Data Synthesis: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD ( P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal ( P = 0.47 > 0.05) nor early childhood ( P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. Conclusions: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.