Aryl hydrocarbon receptor (AhR) is an important environmental chemical sensor. Traditionally, AhR is defined as a transcription factor activated by macromolecular chemicals such as dioxins, and regulating the expression of a variety of genes including metabolizing enzymes. However, recent studies show that AhR can be activated by different types of ligands and regulate a wide range of target genes. Environmental chemicals may affect multiple signaling pathways via AhR, and disrupt cellular homeostasis, resulting in pathologic changes. In this paper, we reviewed the recent progress and mechanisms of AhR-mediated cardiac developmental toxicity, neurotoxicity, carcinogenesis, immunotoxicity, and other toxicities of environmental chemicals. A comprehensive understanding of AhR activation and its toxicity mechanisms may conduce to the prevention and treatment of human diseases caused by environmental chemicals.