The use of chemical compounds has beneficial effects on society in a number of ways but these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds, ranging from instant death to a gradual process of chemical carcinogenesis. Herein, we review the historical aspects of “chemical carcinogenesis” to understand how various studies are carried out and how the chemical substances are causing carcinogenesis, who were dedicated to establishing the association between chemical substances and carcinoma. Cancer has been mentioned by Hippocrates as “karkinos.” Over the years, many researchers starting from Sir Percivall Pott who related occupational exposure to cancer in chimney sweeps, Yamagiwa and Ichikawa, Kennaway, Berenblum and Shubik, Foulds, Rehn, and many others have done a lot of research on chemical carcinogenesis. Today, there is sufficient evidence that exposure to chemical agents is the root cause for most human cancers which theoretically implies that most human cancers are preventable by appropriate management of the human environment. In this article, we are exploring the historical perspective of chemical carcinogenesis.