The XR-750 was developed in response to a 1969 rule change by the American Motorcyclist Association that restructured its Grand National Championship Class C regulations. The previous rules, in place since 1933 and revised in 1954, held an equivalency formula that allowed flathead sidevalve engines up to 750cc displacement while restricting more modern overhead valve engines to 500cc. This formula had kept the older flathead technology competitive and discouraged broader participation. By the late 1960s, the British manufacturers BSA, Norton, and Triumph were selling large-displacement overhead valve motorcycles to the public but had no viable 500cc OHV racing bikes to comply with the existing rules. Under increasing pressure, the AMA changed the regulations to a single 750cc limit regardless of valve configuration, which immediately rendered Harley-Davidson's flathead KR series uncompetitive.
Harley-Davidson's racing manager Dick O'Brien and his team had limited time and budget to respond. Rather than start from scratch, they adapted the existing Sportster-based XLR magneto race engine — originally 900cc — by modifying the stroke and connecting rods to reduce displacement to the legal 750cc limit. These initial iron-head XR-750s of 1970 and 1971 were prone to overheating and insufficient power. A major redesign for 1972 introduced an all-aluminium head and cylinder package with revised bore and stroke dimensions, creating the competitive machine that would dominate the following decades.
The XR-750 used unit construction engine cases splitting vertically into four cavities: a centre front crankcase, a centre rear gearbox, a right-side gearcase for the timing train housing four camshafts, and a left cavity for the primary drive chain. The four-camshaft arrangement, inherited from earlier KR and WL flathead designs, allowed greater flexibility in cam timing and gave pushrods a straighter path to the rocker arms. To comply with AMA homologation rules, 200 examples were produced and offered for sale at Harley-Davidson dealers at US$3,200.
The XRTT road racing variant featured a fibreglass full fairing, a six-gallon fuel tank, a rear disc brake, and a Fontana four-leading-shoe drum brake at the front — the last competition motorcycle produced with a drum front brake before disc brakes became universal. Power output was estimated at between 70 and 79 horsepower from the early 1972 engines, rising to an estimated 100 horsepower or more by the mid-2000s.
Riders on XR-750 machines won 29 of the 37 AMA Grand National Championships held from 1972 through 2008. The motorcycle is associated with the careers of Mark Brelsford, Cal Rayborn, and Jay Springsteen. Its dominance across both dirt track and flat track disciplines — and its longevity as a competitive platform across four decades — gave it a claim as the most successful racing motorcycle in AMA history.
In 1989, Lou Gerencer Sr. constructed a hillclimbing XR-750 with an extended swingarm, mechanical fuel injection, and nitrous oxide, estimating the engine produced more than 150 horsepower. Despite the engine's brief lifespan under that stress, it held together long enough to win the AMA hillclimb championship.
The XR-750 became widely recognised beyond its racing results when stunt performer Evel Knievel adopted it as his primary jump motorcycle from December 1970 through his final professional jump in October 1976. Knievel set most of his jump records on the XR-750, including a 133-foot jump over 14 buses at Kings Island, a world record that stood for nearly 25 years. One of Knievel's XR-750s is held in the Smithsonian's National Museum of American History.
The motorcycle was included in the 1998 The Art of the Motorcycle exhibition, one of the most-attended exhibitions in the Guggenheim Museum's history.
Customer demand for a road-legal XR eventually led Harley-Davidson to introduce the Sportster XR-1000 in 1983, thirteen years after the XR-750 racer debuted. The XR-1000 used XR-750 cylinder heads mated to a Sportster engine and frame. Priced at nearly twice the base Sportster cost, it sold poorly and was discontinued after two years. The XR1200, introduced in Europe in 2008 and the United States in 2009, had less engineering in common with the XR-750 but found a stronger commercial reception.