The Leukemia Cup Regatta started as an event held by the Pine Harbor Yacht Club for the benefit of The Leukemia & Lymphoma Society's Alabama Chapter in April 1988. Funds were raised in memory of a member of the club who lost his life to leukemia, and the Pine Harbor Yacht Club presented The Leukemia & Lymphoma Society (LLS) with a $5,000 at the conclusion of the event.  

The Eastport Yacht Club, in Annapolis, MD, pioneered the concept of competition among boats and crews to raise funds for the fight against blood cancers. Their June 1993 event raised $30,000 for LLS's mission, with the yacht club handling all sailing and water-related logistics. LLS's Maryland Chapter coordinated all land-based fundraising and event activities. A total of 40 boats vied for The Leukemia Cup, presented to the crew that raised the most funds, with other prizes awarded to other fundraising crews and sailors.

Enthusiasm for the event spread across the country into other markets after a presentation at an October 2003 national LLS leadership conference by noted sailing expert and ESPN commentator Gary Jobson, who now serves as The Leukemia Cup Regatta's national chairman. Jobson, a lymphoma survivor, is actively involved with LLS to help organize other Regattas and recruit sponsors and participants on the national, regional and local levels. 

In 2009, the sailing community raised more than $3.8 million at 38 Regattas, bringing the overall campaign results to more than $31 million. More than 9,600 participants took part in the 2008 series.

Sailing World magazine is again serving as the media sponsor of The Leukemia Cup Regatta and will run a series of full-page ads promoting the series throughout 2010, with additional ads to run in Cruising World. Other national sponsors include West Marine, Mount Gay Rum, North Sails, John Mecray and Ken Gardiner.