The 24-year-old Spaniard lost control of his bike on turn 12 of the Barcelona circuit. No other riders were involved but pictures indicated that Salom's bike left the track at high speed in the corner, which has an asphalt run-off section rather than a gravel trap.
Rider and bike collided with airbags at the edge of the circuit with little to slow them down.
Medics reached the scene of the accident within minutes, where Salom was found to be in cardiac arrest.
A statement from MotoGP's medical director detailed frantic efforts to save him: "CPR continued at the trackside for 18 minutes, but taking into consideration Salom's life threatening condition, a decision was taken to transport him by road in an ambulance," it said. "Treatment continued for an additional 40 minutes during the ambulance transfer, but oxygen saturation deteriorated."
After further emergency treatment at Barcelona's Hospital General de Catalunya, Salom was pronounced dead at 4:55pm local time.
Tributes to the young rider poured in from both inside and outside the sport. Former F1 world champion Fernando Alonso wrote on Twitter: "Such awful news. Such anger and sadness. Rest in peace, rider. A huge embrace to Luis Salom's friends and family."
Tennis star and fellow Spaniard Rafael Nadal also paid tribute: "Very sad news. Although words cannot give comfort in times like these, all my support goes to Luis Salom's family and friends."
Salom was one of the sport's bright young stars and had enjoyed considerable success in the Moto3 class. After making his World Championship debut at Jerez in 2009 he reached the podium in 25 races, including nine victories in the Moto3 class.
In 2012 he was runner up in the Moto3 class behind Sandro Cortese and ahead of Maverick Vinales. A year later he was third in a battle with Vinales and Alex Rins that went to the final round of the championship. He also clinched three podiums in the Moto2 class, including second place at this season's opening race in Qatar.
The Catalunya race meeting continued on Saturday with riders following the track layout used by Formula 1, which eliminates the corner where the accident occurred.
Salom was a popular figure in the close-knit MotoGP paddock, known for his smiling demeanour and passionate displays of emotion on podium and track. Many riders added stickers with black ribbons and Salom's nickname 'El Mexicano' to their bikes in tribute.
In spite of the sport's obvious dangers, MotoGP's safety record is good. Salom's death is the first since Italian Marco Simoncelli lost his life in 2011's Malaysia MotoGP, and the championship has worked hard to improve both medical facilities and rider safety.