York was born in Muskogee, Oklahoma. The son of John Clement York, a dentist who died when York was 15, York grew up in Little Rock and attended local schools until college. He graduated from the University of Notre Dame in South Bend, Indiana in 1971. He received a doctorate in blood pathology from Stritch School of Medicine at Loyola University Chicago in 1975, and engaged in seven years of post-doctoral study, specializing in the laboratory diagnosis of lymphoma and leukemia.
York left academia to establish DeYor Laboratories in Boardman, Ohio. In 1993, he sold DeYor Laboratories to Corning Inc. York has made a number of contributions in the medical field, having given a $1.5 million contribution to establish an Endowed Chair in Pathology and an Endowed Chief Residency in Pathology at the University of Arkansas for Medical Sciences. In 1999, he donated a science and math building to Catholic High School for Boys, his alma mater. He also joined Jerry Jones and an anonymous donor in donating $10 million to the school.
On December 28, 2008 John and Denise York announced that their son, Jed York, would become team president and operating head of the franchise, while they would become co-chairpersons responsible for providing resources and maintaining their role of interacting with other owners and NFL executives. John continues to serve as chairman of the NFL's International Committee and also sits on the league's Audit and Business Ventures Committees.
On 24 May 2018, the York family via 49ers Enterprises bought shares in English soccer club Leeds United to become a minority investor, the 49's Enterprises is the business arm of the NFL side San Francisco 49ers.
- San Francisco Gate: "The Family Business / 49ers owner talks of her brother, her privacy and her priorities" by Nancy Gay September 1, 2000
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- Brantley, Max (October 10, 2013). "Little Rock Catholic High gets $10 million gift from Jerry Jones, John York and anonymous donor". Arkansas Times. Retrieved September 9, 2018.
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