Founded by entertainer Danny Thomas in 1962, it is a 501(c)(3) designated nonprofit medical corporation which focuses on children's catastrophic diseases, particularly leukemia and other cancers.

[9] He prayed for intercession to Saint Jude Thaddeus for a means to provide for his family, and about a week later, he obtained a gig that paid 10 times what he had put in the offering bin.

[10][7] While some donations for St. Jude come from government grants and insurance recoveries, the principal source of funding comes from the American Lebanese Syrian Associated Charities (ALSAC), a semi-independent entity founded in 1957 by Danny Thomas.

Danny's daughter Marlo Thomas grew up supporting the mission of St. Jude Children's Research Hospital, and she became its national outreach director in 1991.

[18] St. Jude has an International Outreach Program to improve the survival rates of children with catastrophic illnesses worldwide.

As of July 2023, the Domestic Affiliate Clinic sites include: St. Jude also works with Le Bonheur Children's Medical Center, also located in downtown Memphis.

Both St. Jude and Le Bonheur are teaching hospitals affiliated with the University of Tennessee Health Science Center.

University of Tennessee physicians training in pediatrics, surgery, radiology, and other specialties undergo service rotations at St. Jude.

[27][28] A commitment has been made to establish a US$412 million research facility in Memphis, Tennessee, one purpose of which will be to serve as a collaborative hub.

[23] St. Jude Children's Research Hospital and American Lebanese Syrian Associated Charities (ALSAC) are both nonprofits.

[33] In 1995, St. Jude received an anonymous letter postmarked in Dallas, Texas, containing a $1 million winning McDonald's Monopoly game piece.

[36] Peter C. Doherty, Ph.D., of St. Jude Children's Research Hospital was co-recipient of the 1996 Nobel Prize in Physiology or Medicine for work related to how the immune system kills virus-infected cells.