Objectives: The objective of the study was to characterize the electroencephalogram (EEG) changes associated with different antipsychotic medications based on the evidence from the literature. Methods: A systematic search of the databases Medline, PsycINFO, and PubMed was conducted. The Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the construction of this systematic review. Primary research articles that reported descriptive EEG results, included comparisons of subjects with and without antipsychotic therapy, and excluded patients with epilepsy were included in the analysis. The outcome was the presence of epileptiform discharges or slowing on EEG. We analyzed pooled data, where possible, from studies with a similar intervention and methodology. Results: Fourteen articles reporting on a total of 665 patients were reviewed. Among the publications, clozapine was the drug most consistently accompanied by EEG slowing and epileptiform discharges, with an odds ratio of 16.9 (95% confidence intervals (CI): 5.4 to 53.2) and 6.2 (95% CI: 3.4 to 11.3), respectively in the analysis of pooled data. Only one study reported a significant increase in epileptiform discharges with phenothiazine antipsychotic therapy as a group, but the impact of individual drugs was not analyzed separately. Conclusions: This systematic review suggests that, among antipsychotics, clozapine most frequently induces EEG slowing and epileptiform discharges. There remains limited data with respect to other individual antipsychotic agents and covariates including drug dose, plasma levels, dose adjustments, and treatment duration that influence EEG changes.