Coulthard entered Formula One with Williams in 1994 as a replacement for the late Ayrton Senna and won his first Grand Prix in Portugal in 1995. He joined McLaren for 1996 and remained there through 2004, partnering Mika Häkkinen through the team's dominant 1998 season when McLaren won the Constructors' Championship.
His career best championship result came in 2001, when he finished second in the Drivers' Championship — 58 points behind World Champion Michael Schumacher — winning races in Brazil and Austria and collecting four further podiums later in the year. Coulthard won the Hawthorn Memorial Trophy four consecutive times between 1998 and 2003 as the most successful British driver in Formula One each season.
He moved to Red Bull Racing in 2005 and secured the team's first podium with a third place in Monaco in 2006. Coulthard announced his retirement from Formula One ahead of the 2008 British Grand Prix, finishing his career with 13 wins, 12 pole positions, 18 fastest laps, and 62 podium finishes across 246 starts.
On 4 April 2010, Coulthard announced a return to active competition by signing with Mücke Motorsport in the Deutsche Tourenwagen Masters. He was partnered throughout the three seasons by Maro Engel (2010 and 2011) and then Robert Wickens (2012).
In his first DTM season (2010), Coulthard described the year as his "apprenticeship," finishing 16th in the Drivers' Championship with a single point. The 2011 season showed incremental improvement, with his sole points finish coming at the Norisring where he finished eighth. Despite finishing every remaining race, a disqualification at Ricardo Tormo — his car's rear wing was incorrectly mounted during qualifying — cost him further ground. He again finished 16th in the championship with one point.
The 2012 season proved his strongest in DTM. Coulthard opened with an eighth-place points finish at the Hockenheimring and followed it with a fifth-place result at the Norisring. Before the final round at Hockenheim, he announced his retirement from racing to spend more time with his family and focus on his media commitments. He finished 15th in the final Drivers' Championship with 14 points.
Following his Formula One retirement, Coulthard joined the BBC as a pundit and co-commentator alongside Martin Brundle for their Formula One coverage. In 2016 he moved to Channel 4 when they acquired terrestrial rights to the sport. He co-owns Whisper Films, the production company that produces Channel 4's Formula One coverage. In 2019, Coulthard was elected president of the British Racing Drivers' Club.
Coulthard also excelled in the Race of Champions, finishing runner-up in the Drivers' Cup in 2008 and winning the competition outright in 2014 and 2018. He was appointed Member of the Order of the British Empire (MBE) in the 2010 Birthday Honours for services to motorsport.
Coulthard's DTM stint, though modest in results, illustrated his appetite for competition beyond Formula One. His Formula One career — defined by the McLaren years alongside Häkkinen and the championship runner-up finish in 2001 — places him among the most successful British drivers of his generation. His subsequent prominence as a broadcaster has kept him among the most recognisable faces in motorsport.