Wheeler was born in Belmont, North Carolina. He began his promotional career at age nine, selling tickets for a bicycle race. He was a defensive lineman for the South Carolina Gamecocks in the late 1950s. His teammates included Future NASCAR communications Director Jim Hunter (a running back), and Jim Duncan (later known as a marketing executive at Lowe's Motor Speedway). Early in Humpy's career, he was the race tire rep.for Firestone Tire and represented them at the Indy 500 for several years and helped them achieve an incredible winning record that stands today.

Recently, in an off-track but still Automotive related pursuit, Wheeler provided the voice for "Tex," a 1975 Cadillac Coupe de Ville cartoon character, in the 2006 Pixar hit film Cars.

After becoming the President of Charlotte Motor Speedway, Wheeler earned the reputation for organizing publicity Stunts. A few weeks after driver Cale Yarborough gave the less-than-complimentary nickname 'Jaws' to rival driver Darrell Waltrip, Wheeler bought a giant dead shark, placed a dead chicken in the shark's mouth, and had it driven around the track on a flatbed truck before a race at Charlotte (Yarborough's sponsor at the time was Holly Farms Poultry). In 1984, the pre-race show for the World 600 was a reenactment of Operation Urgent Fury, the invasion of Grenada the previous year.

Wheeler has a personal record of picking the correct winner of the NASCAR Sprint All-Star Race 10 of the last 19 years. In 2000, much to the dismay of Dale Earnhardt Sr. Wheeler picked Cup rookie Dale Earnhardt Jr. to win and Earnhardt Jr. went on to become the first rookie to win the event. In 2005, he picked Mark Martin and Martin won the race. In 2006, he picked Carl Edwards to win, but Edwards finished fourth (behind winner Jimmie Johnson). He picked Johnson to win the 2007 event, but Johnson finished second to Kevin Harvick. He again chose Edwards to win the 2008 event, but Edwards finished 10th; Kasey Kahne won the race.

Wheeler was inducted into the International Motorsports Hall of Fame on April 27, 2006 and to the Motorsports Hall of Fame of America on August 12, 2009.

In 2007, Wheeler announced that the Bank of America 500 would feature an "all-you-can-eat grandstand," where fans would pay a set ticket price, and would then get to eat as much as they wanted of the grandstand's food before, during, and after the race. The publicity for this event included Nathan's Hot Dog Eating Contest champion Joey Chestnut at the press conference.

On August 18, 2008, Wheeler announced the formation of The Wheeler Company, a consulting management firm focusing on general Business, professional Sports, and motorsports. Wheeler serves as chairman, with his son Howard III ("Trip") serving as President.

Although he had announced that he would step down as President and General Manager of Lowe's Motor Speedway soon after the race, Wheeler had hopes of staying on as a part-time consultant especially in light of the upcoming 50th anniversary of the Speedway in 2009. However, apparently due to a falling out with Bruton Smith for reasons yet unknown, Wheeler's lengthy association with Lowe's Motor Speedway was unceremoniously ended. Smith thereafter wasted no time in appointing his son, Marcus Smith, as the new President and General Manager of the Speedway.

In October 2011, Wheeler was announced as one of the principals behind the Grand Prix of America, a Formula One race to be run in New Jersey starting with the 2014 Formula One season.

In the fall of 2013, Wheeler once again made auto racing news as he announced the foundation of Speedway Benefits, a marketing and advertising partnership seeking to combine short-tracks across the United States into a single body for the purposes of contract negotiations with suppliers, advertisers, and Business partners. Seeing such an alliance as a way to strengthen the bargaining positions of racetrack owners and to stymy the increasing power of NASCAR in North American auto racing, the organization seeks to "grow grassroots racing." By combining more than 1000 short track venues across North America into a collective body, Speedway Benefits argues that the purchasing power and fan base of short track racing exceeds that of other, established national Sports leagues, thus potentially enabling short track owners to bargain more effectively and to pursue national level sponsorships of local and regional venues.