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Tigrett belonged to a well-to-do business family. He was raised in Tennessee until the age of fifteen. He is an alumnus of Centre College, which later gave him an honorary degree (in 1997) for promoting African American culture and racial harmony.
On June 14, 1971 he and Peter Morton started the first Hard Rock Café (HRC) restaurant in London's fashionable Mayfair district. The restaurant combined rock music, memorabilia related to rock 'n' roll and American cuisine. The cafe-music-museum concept became very popular and soon the restaurant opened units in different parts of the globe. HRC was the first theme restaurant chain in the world. Tigrett bought Morton out, and took on the original Cafe in London along with rights to the name in most of the world including the U.S. states East of the Mississippi; Morton had rights to the name in states West of the Mississippi and in Israel, Colombia and Australia.
Eventually both sold their interests in HRC to the Rank Organisation.
In 1992, Tigrett started the House of Blues (HOB) with partner Dan Aykroyd and designer James Cafarelli. Harvard University was an initial investor in the business and a prototype was opened in Cambridge, Massachusetts. Soon after Disney and Andrew Filipowski invested in the venture. Differences of opinion between Tigrett and the other HOB board members over operations resulted in Tigrett leaving the venture in 1998.
In the late 1990s, Tigrett launched The Spirit Channel, an enterprise offering services related to spirituality and health through the Internet, traditional media and physical locations. The venture failed to take off. In 2004, Tigrett launched yet another new venture, the Bozo Project, focusing on the restaurant business.
Tigrett was influenced by his guru, Sathya Sai Baba. In the BBC documentary The Secret Swami Tigrett stated that he believed that there was truth to the rumors of Sai Baba's actions of pedophilia and sexual abuse towards some of his young male followers. He also stated that such behavior would not change his belief in Sai Baba.
In 1989 Tigrett married Maureen Cox Starkey, the ex-wife of Beatle drummer Ringo Starr. She died of leukemia in 1994. With great affection Isaac often introduced her as "My most authentic piece of rock and roll memorabilia." Their daughter, Augusta King Tigrett, was born January 4, 1987 in Dallas, Texas.
- Buncombe, Andrew "Hard Rock Cafe: The tribe that bought a billion dollar business", The Independent, December 12, 2006
- The Secret Swami Transcript, BBC, June 17, 2004