The Aryl Hydrocarbon Receptor (AHR) is a multifaceted transcription factor involved in xenobiotic metabolism, immune cell development, and epidermal differentiation. AHR is activated by aryl hydrocarbons, of which TCDD is well-known. Coal tar (CT) is an activator of AHR and is used in the clinic as a treatment for atopic dermatitis. To better understand AHR activation and downstream effects, we studied ligand-mediated DNA binding by AHR, its target gene transcription, and overall differentially expressed genes in treated keratinocytes. TCDD and CT treated human primary keratinocytes were subjected to chromatin immunoprecipitation followed by deep-sequencing (ChIP-seq) and RNA-sequencing to study genomewide effects of AHR activation by both AHR ligands. TCDD and CT, as AHR ligands, show early (after 2 hours) upregulation of genes involved in detoxification pathways. Also, we found an upregulation of important genes encoding terminal differentiation proteins (IVL, FLG), antimicrobial proteins (e.g. PI3, SLPI, S100A8), and tight junction proteins (CLDN4, OCLN), approximately 24 hours after AHR activation by CT and TCDD.The genomic binding of the AHR indicates that the canonical cellular responses after CT and TCDD exposure steer primarily towards activation of xenobiotic metabolism pathways. The transcriptional analysis shows additionally differentially regulated genes in the aforementioned metabolism pathways, and the activation of the antimicrobial defense mechanism of the epidermis. The latter may influence the interaction between host and microbes and could have important implications for the skin microbiome composition in coal tar treated AD patients.