Panoz was born into an Italian-American family; his father Eugene Panunzio had emigrated from Avezzano, Italy, and shortened the family name to Panoz after arriving in the United States. Don attended Greenbrier Military School in Lewisburg, West Virginia, where he met his future wife Nancy. The couple served together in Japan with the United States Army before settling in Pittsburgh.
While studying business at Duquesne University, Panoz operated two drug stores in Pittsburgh. In 1961 he co-founded Milan Pharmaceuticals with Milan Puskar in White Sulphur Springs, West Virginia; the company was later renamed Mylan and grew into one of the largest generic-drug manufacturers in the world. Panoz led a research group that pioneered time-release drug delivery through a transdermal patch — a technology that became most widely recognised in the nicotine patch. When Mylan declined to commercialise the invention, Panoz departed in 1969 and relocated his family to Ireland, where he established Elan Corporation. Elan became an industry leader in drug-delivery products and was the first Irish company to list publicly on a United States stock exchange; it was eventually acquired by Perrigo in 2013.
With the wealth generated by these ventures, Panoz diversified into hospitality and leisure, co-founding Chateau Elan Winery and Resort in Braselton, Georgia in 1992, and developing resort and golf properties in California, Scotland, and Australia.
Panoz's entry into motorsport began in 1989 when he funded a fledgling company his son Dan had started, called Panoz Auto Development. The elder Panoz was initially sceptical of the venture but brought his business connections to bear, enlisting figures such as Mario Andretti to lend credibility and expertise to the project. The ambition was to build a sports car capable of competing at the 24 Hours of Le Mans.
Panoz Motorsports was formally established in 1997 in Braselton, Georgia, and entered the 24 Hours of Le Mans that same year with the newly developed Panoz Esperante GTR-1. The car's performance was notable for an American privateer effort: it finished ahead of all but two of the major factory entries in its class, immediately establishing the Panoz name in top-level endurance racing.
The most lasting institutional contribution of Panoz to motorsport was the founding of the American Le Mans Series (ALMS) in 1999. The series was conceived to transplant the European-style multi-class endurance sports car racing format — most famously embodied by Le Mans — to the Americas. Running events at circuits across the United States, the ALMS filled a gap left by the declining IMSA GT Championship and introduced American audiences to the prototype and GT categories familiar from the ACO's French showcase. The series operated independently for over a decade and was a key driver of manufacturer investment in sports car racing in the region before merging with the Grand-Am Road Racing Series to form the unified United SportsCar Championship in 2014.
Panoz also held long-term leases on significant North American racing venues, including Sebring International Raceway, Road Atlanta, and Mosport International Raceway, all of which were subsequently sold to NASCAR's IMSA Holdings.
Don Panoz died on September 11, 2018, at the age of 83, following a battle with pancreatic cancer. He and Nancy had been married for 63 years and had six children. His career traced an unusual arc: pharmaceutical pioneer, transdermal drug-delivery inventor, winery and resort developer, and ultimately one of the most influential private backers of American sports car racing in the modern era. The ALMS he founded gave a generation of fans and competitors a world-class endurance racing platform on home soil, and the Panoz marque he supported at Le Mans remains a rare example of an American sports car built to challenge the European factory establishment in prototype-class racing.