At the season-ending IZOD IndyCar World Championship at Las Vegas Motor Speedway, Wheldon was killed in a collision with a fence post alongside the circuit on the race's eleventh lap.

[24] He competed in the U.S. F2000 National Championship in 1999 in Jayhard/Primus Racing's Van Diemen Ford RF99 car, achieving six wins and eleven top-ten finishes to become the first British and European series champion.

[26] Wheldon's early performance was affected by jet lag from constant travel to the United Kingdom to visit his family and his desire to compete in Formula Three.

[15][37] The lack of sponsorship prevented him from starting the season though he was called up to drive when regular driver Dario Franchitti broke his vertebrae in a motor bike accident in Scotland.

27 Dallara IR-03 Honda HI3R V8 car, at the Indy Japan 300 at Twin Ring Motegi, Wheldon qualified fifth and finished the accident-shortened race seventh.

[58] Two races later, at Chicagoland Speedway, he led a race-high 88 laps to surpass Hornish's series record with his sixth win of the year.

[59] Wheldon won the championship before starting the season's penultimate round by setting a single practice lap of Watkins Glen International.

[63] CGR resigned Wheldon for the 2006 season and the team changed manufacturers from Panoz to Dallara and engine suppliers to Honda after Toyota withdrew.

[72] He began the season with pole position at the season-opening XM Satellite Radio Indy 300 at Homestead–Miami Speedway, and led 177 of 200 laps to win his third successive event at the track, a new series record.

[74] After qualifying sixth for the Indianapolis 500, he retired from the rain-shortened race after a late-event collision with Marco Andretti, losing Wheldon the lead of the drivers' championship.

Foyt 225 at Milwaukee Mile was overshadowed by a physical confrontation with Patrick following a collision on the 88th lap;[76] the two reconciled after a private meeting with IndyCar president Brian Barnhart.

[79] Wheldon won the RoadRunner Turbo Indy 300 at Kansas Speedway three races later, becoming IndyCar's first driver to claim two consecutive victories at the track.

[81] As IndyCar had become more orientated towards road and street circuits following the merger of it and the Champ Car World Series, his performance diminished in the remaining races since his driving on such tracks were not as good as on ovals.

[84] On 2 September, CGR announced that Wheldon would be released from his contract at the end of the season as Dario Franchitti left NASCAR and returned to IndyCar.

[18][21] He filed a $383,400 lawsuit against Barnes in Marion County Superior Court on 18 August for late payment of his salary and of his share of earnings from his on-track achievements as well as taxation issues.

[98] Talks with several teams, including with Dreyer & Reinbold Racing co-owner Robbie Buhl to share a car with Mike Conway fell through.

[101] He then became a color commentator and pit lane reporter for the cable television channel Versus (now NBCSN) for three IndyCar Series events (Iowa, Texas and Toronto), believing he would not race again in 2011.

[87][103] Wheldon was also employed by IndyCar, car manufacturer Dallara and designer Tony Cotman to test and develop the official prototype model of a new one-specification chassis that debuted at the beginning of the 2012 season.

[111] In 2006, Wheldon returned to compete in the season-opening 24 Hours of Daytona for Chip Ganassi Racing with Scott Dixon and Casey Mears in the DP class.

[113][114] Wheldon returned for a fourth time to participate in the 24 Hours of Daytona for Chip Ganassi Racing with Dixon, Alex Lloyd and Salvador Durán.

[118] Wheldon was also ABC's in-race reporter and spoke in defence of his participation in the event and IndyCar to the network's commentary team during the warm-up laps.

Attempting to avoid the crash ahead, Vítor Meira lost control, spinning inward collecting both Charlie Kimball and E. J. Viso.

He collided with a fence post along his car's right-hand side, creating a deep defect in the chassis that went from the upper pedal bulkhead and through the cockpit.

He was extricated from his car by the trackside safety team and airlifted to the University Medical Center of Southern Nevada for his critical injuries.

A five-lap, three-wide formation salute was held in Wheldon's honour, along with "Danny Boy" and "Amazing Grace" played on the bagpipes in the background.

[103][121] An autopsy conducted by the Clark County Coroner Michael Murphy on 17 October determined that Wheldon died of a blunt trauma to his head.

"[18] Although he had a brash and confident persona that made him "cocky yet likeable",[129] journalist Maurice Hamilton noted that Wheldon was seen by many as "a devoted family man, deeply respected and universally liked despite, or perhaps because of, a cheeky sense of self-awareness and a clever cultivation of his image".

[133] A charity race in Wheldon's honour was held in Milton Keynes on 6 December with drivers such as Franchitti, Jenson Button and Anthony Davidson competing.

[139] A memorial plaque featuring his likeness and career achievements was unveiled in St. Petersburg outside the second turn of its street track in March 2013 and a wall in which each of the winners of the race was etched.

[142] During the 2016 Kobalt 400 at Las Vegas Motor Speedway, pit lane reporter Jamie Little and motorsport publicist Brent Brush placed a Dan Wheldon Memorial plaque outside turn two, near the point where he was killed.