Jefferies was born in Shipley, West Yorkshire, into a motorcycle racing family. His father, Tony Jefferies, was a TT race winner in 1971, and his uncle Nick Jefferies was also a TT winner. He attended Salt Grammar School before embarking on a professional racing career. The depth of the family's racing tradition shaped Jefferies's own path from an early stage.
Jefferies competed across a broad range of classes and championships during his career. He entered Grand Prix world championship competition in 1993 and also contested the World Superbike Championship in 1993 and 1995. In British domestic competition he became British Superstock 1000 champion on two occasions in the three years preceding his death.
His true calling, however, was street circuit racing on the island roads of the Isle of Man and the public roads of the North West 200 in Northern Ireland, where he was a four-time winner. At the TT he became a rider of extraordinary calibre: he was the first competitor to lap the 37.73-mile Snaefell Mountain Course at more than 125 mph, and the first to win three TT races in a single week in three consecutive years. During the 2002 Senior TT he set the outright lap record for the course at 17 minutes 47 seconds — an average speed of 127.29 mph (204.85 km/h) — which stood as the benchmark at the time of his death.
On 29 May 2003, during practice week for the 2003 Isle of Man TT, Jefferies was killed at the Crosby section of the course. The Crosby turn is a shallow left-hander taken at approximately 160 mph, with stone walls bordering the gardens on the outside. Jefferies was riding his TAS Racing GSX-R1000 Suzuki following a lap averaging 125 mph — the fastest in that practice week — when his machine struck the wall at number 29 Woodlea Villas. The impact hurled Jefferies and his motorcycle across the circuit, bringing down a telephone pole and scattering debris across the road. He was killed instantly.
Fellow competitor Jim Moodie, unable to brake in time when he arrived at the scene, rode into telegraph lines that had fallen across the road; three snapped under his motorcycle but one looped over the windscreen and briefly wrapped around his throat before breaking. Moodie survived but retired from TT competition shortly after. John McGuinness, one of the first riders on the scene and a close friend of Jefferies, described it as looking like a war zone.
The TT organisers issued a formal statement later that afternoon announcing Jefferies's death and confirming an immediate inquiry. The inquiry became contentious: organisers maintained marshals had acted correctly, while riders argued that insufficient warning flags had been displayed and that those shown did not adequately signal the severity of the incident. A parade lap in Jefferies's honour was held at the end of the TT weekend, with thousands of motorcycles filling the 37-mile course.
David Jefferies left behind a record that marked him as one of the greatest road racers of his generation. His consecutive hat-tricks at the TT between 1999 and 2002 — nine wins across those four events including six in successive years — placed him in elite company in the sport's history. The absolute lap record he set in 2002 underscored how far ahead of the field he had become on the island roads. He was 30 years old at the time of his death, and the TT community mourned not only the racer who had already achieved so much but the titles and records that might yet have followed.