The McArdle Laboratory for Cancer Research was established in 1940 as one of the first basic cancer research facilities in the world. The foundation for the development of the Laboratory and the University of Wisconsin's program in experimental cancer research was made possible by the generous donations of private citizens.

In the 1930s, a bequest in the will of Jennie Bowman established the Jonathan Bowman Memorial fund in memory of her father, a prominent state senator. This fund provided the seed money for the initiation of a cancer research program at the University of Wisconsin in Madison. The Bowman funds initially were allocated for fellowships to promising young investigators interested in studying cancer. One of the Bowman Fellows, Dr. Harold P. Rusch, became the first Director of the McArdle Laboratory and established the cancer research program at the University of Wisconsin.

The construction of the first McArdle building resulted from a bequest by Michael W. McArdle, a prominent Chicago industrialist and attorney from Door County Wisconsin. Expanded facilities, funded by the National Cancer Institute, were provided by the construction in 1964 of the present McArdle Laboratory.

Serving as the Director until 1972, Dr. Rusch (with help from Associate Director Dr. Van R. Potter) charted the course for the Laboratory's scientific future by recruiting a staff of talented young scientists, whose creativity and productivity soon earned the McArdle Laboratory an international reputation for excellence in cancer research. In 1973, Dr. Rusch established the University of Wisconsin Comprehensive Cancer Center, the clinical research complement to the McArdle Laboratory. From 1972-1991, Dr. Henry C. Pitot, a prominent pathologist and oncologist, provided the leadership as the center expanded its program. Dr. Elizabeth C. Miller, who with her husband and scientific partner, Dr. James A. Miller, laid the groundwork for the field of chemical carcinogenesis, also played a key leadership role in the administration of the center, serving as the Associate Director of the Laboratory from 1973 until her death in 1987. In 1992 Dr. Norman R. Drinkwater assumed the directorship, and Dr. Bill Sugden became the Associate Director of the McArdle Laboratory. The McArdle and Comprehensive Cancer Center NCI cancer center support grants were consolidated under Dr. John Niederhuber in 2001. In 2006, Dr. F. Michael Hoffmann took over as Associate Director and in 2008 assumed the Interim Directorship after Dr. Drinkwater stepped down as Director. From September 1, 2009 until August 31, 2014 Dr. James D. Shull was the Director of the McArdle Laboratory. On September 1, 2014 Dr. Paul F. Lambert became the new Director of the McArdle Laboratory.

In its early years, a major focus of McArdle's research program centered on studies of chemical carcinogenesis. McArdle scientists established the basis of the chemical induction of various cancers and discovered how known carcinogens initiate the genetic changes in cells that result in tumor formation. Early studies also focused on the biochemistry of cancer cells and how they differ from normal cells. Gradually the focus of the research program was expanded to other areas of cancer research including the role of viruses in the causation of cancer and, more recently, the roles of oncogenes and developmental processes in cancer.

For additional information about the history of the McArdle Laboratory and cancer research at the University of Wisconsin-Madison, see "Something Attempted, Something Done", by Harold P. Rusch, University of Wisconsin Medical Alumni Association, 1984.