Whitham developed as a racer through British domestic competition, claiming the 1986 British 80 cc Championship and the 1988 1300 cc Production British Championship before becoming a consistent front-runner in the senior Superbike classes. He also competed at the Isle of Man — entering the Manx Grand Prix in 1985 and the TT from 1986 to 1989, recording three top-six finishes. He won races at Superstock, Seniorstock, Supersport 600, and TT Formula One levels.
In 1993 he was at the peak of his British form, winning both the British Superbike Championship Supercup and the ACU TT Superbike British Championship for Yamaha. He had previously won the 1991 MCN TT Superbike Challenge with Suzuki and the 1988 Mallory Park Race of the Year. He also made a one-off 500 cc Grand Prix appearance at the 1992 French Grand Prix at Magny-Cours.
In 1994, Whitham stepped up to the Superbike World Championship full-time with Ducati, sharing the team with Carl Fogarty. He won at Sentul and finished seventh overall, a solid debut at the world level. Returning to Britain in 1995, he was leading the British Superbike standings when he was diagnosed with Hodgkin lymphoma mid-season. The diagnosis ended his championship campaign but he still made a wildcard World Superbike appearance at Brands Hatch, taking a podium.
His recovery was swift enough for him to compete in 1996, and the result was exceptional. Riding for Yamaha in the British Superbike Championship, he finished runner-up despite missing points at the opening round, winning ten races — twice the number scored by champion Niall Mackenzie. Motorcycle News recognised this comeback with the Man of the Year award for the second time.
Whitham joined the Harris Suzuki team for the 1997 and 1998 World Superbike seasons, finishing eighth in the championship in both years with a combined three podiums. When the factory contract changed ownership for 1999, the new team chose different riders, leaving Whitham without a World Superbike berth. He briefly joined Kenny Roberts' Modenas team in the 500 cc World Championship but suffered a heavy crash at Brno, breaking his pelvis.
He made a one-off return at Donington in 1999, winning the race, and then committed fully to the Supersport World Championship from 2000 to 2002. He won on his very first outing in 2000 and finished eighth overall, though a sequence of crashes during the season blunted his early momentum. In 2001 he was fourth overall and in 2002 he won in wet conditions at Silverstone. Later that year, however, he was diagnosed with glaucoma — most likely a consequence of the chemotherapy he had undergone years earlier — and was forced to retire from racing at the season's end. His Supersport career totalled four wins and twelve podiums, and he held the Supersport lap record at Donington Park until 2007.
After retiring, Whitham established a second career as a television commentator and analyst, working for Eurosport, Channel 4, and ITV. He became a regular voice on ITV4's Isle of Man TT coverage alongside former racer Steve Parrish, with the broadcasts also broadcast on the Velocity Channel in the United States. He contributed road tests to the British motorcycle magazine Visordown and worked with young riders in the Virgin Media Cup. In 2008 he published his autobiography, "What A Good Do!". He was awarded an honorary Doctorate by Huddersfield University in July 2009.
In May 2017, Whitham confirmed on his personal website that his earlier cancer had recurred and that he was undergoing chemotherapy and further treatment. By 2018 his condition required intensive in-patient treatment at a hospital in Leeds, preventing him from appearing in TT coverage that year. Whitham also operates Crosland Moor Airfield, a small private airstrip near Huddersfield.
Whitham's career is remembered both for its competitive accomplishments and for the personal resilience it demonstrated. Twice recovering from serious health episodes — Hodgkin lymphoma in 1995 and the later cancer recurrence — while still winning races at world level made him one of the most respected figures in British motorcycle racing. His work as a television analyst has kept him central to the sport's coverage long after his riding career concluded.