Pritzker was born to a Jewish family in Chicago, Illinois, the son of Marian "Cindy" (née Friend) and Jay Pritzker. Pritzker graduated with a B.A. from Menlo College. His Father Diversified the Chicago-based family Business, the Marmon Group - along with his brothers Robert Pritzker and Donald Pritzker - building it into a portfolio of over 60 Diversified industrial corporations. He also created the Hyatt Hotel chain in 1957 and owned Braniff Airlines from 1983–1988. The family has been divesting its assets: in 2006, the family sold Conwood, a smokeless tobacco company, for $3.5 billion to cigarette company Reynolds American Inc; in 2007, the family sold control of the Marmon Group to Warren Buffett's Berkshire Hathaway for $4.5 billion; and in 2010, the family sold its majority stake in Transunion, the Chicago-based credit reporting company, for an undisclosed amount to Chicago-based private-equity firm Madison Dearborn Partners.

In 1972, Pritzker started his career working in the family Business, Hyatt Hotels, where in 1984, he rose to become Managing Director and Divisional Vice President. In 1988, he left Hyatt to pursue his own entrepreneurial activities including become a founding member of Ticketmaster. In 1996, he formed Mandara Spa, a chain of 72 resort spas, which he hoped to pair up with Hyatt Hotels, but ended up being located entirely in competitors to Hyatt. In 2000, 40% of the company was sold to Shiseido Co. In 2001, the remaining 60% was sold to Steiner Leisure Limited, a Nasdaq (STNR) listed company. In 2005, Pritzker founded the private equity firm Geolo Capital with his Mandara Business partner Tom Gottlieb; Geolo Capital focused on Investments in hospitality, entertainment, and health & wellness companies. In 2010, he sold his ownership interest in Hyatt to his family. Geolo Capital purchased a majority interest in the Joie de Vivre boutique hotel chain. In October 2011, he merged the 30 hotel Joie de Vivre chain with the Pomeranc family's 12 hotel Thompson Hotel Group to form Commune Hotels & Resorts which he co-chairs with Jason Pomeranc. In 2012, Commune operated 46 hotels and had $450 million in revenues. In January 2016, Commune Hotels merged with Destination Hotels, where Pritzker serves as co-chairman. With the recent merger the new company has over 97 hotels across six brands and annual revenues of over $2.3 billion.

Pritzker is married to Lisa Stone and they have three children. Pritzker donated $15 million to the University of California at San Francisco for new pediatric emergency room facilities at the UCSF Benioff Children's Hospital. The Lisa and John Pritzker Family Fund funds programs focused on children's health and education, civic activities, and Jewish affairs. In 2016, the San Francisco Museum of Modern Art completed a $500 million expansion, which includes the Pritzker Center for Photography.