The cancer center was first established at Northwestern University in 1974. In 1991 the center was dedicated as the Robert H. Lurie Cancer Center of Northwestern University through a gift of endowment from Ann and Robert H. Lurie. The center's title was modified in 1997, when the National Cancer Institute (NCI) awarded the Lurie Cancer Center the highly competitive "comprehensive" designation — reflecting the center's dedication to the highest standards of cancer research, patient care, education, and community outreach.

Today, the Lurie Cancer Center is one of only 41 NCI-designated "Comprehensive" cancer centers in the nation. In addition, the Lurie Cancer Center is a founding member of the National Comprehensive Cancer Network (NCCN), an alliance of 23 of the world's leading cancer centers dedicated to improving the quality and effectiveness of care provided to patients with cancer.

The Lurie Cancer Center is affiliated with four teaching hospitals in Chicago —Northwestern Memorial Hospital,Ann & Robert H. Lurie Children's Hospital of Chicago , theRehabilitation Institute of Chicago, and the Jesse Brown Veteran's Affairs Medical Center, treating more than 10,000 new cancer cases each year.