The crash occurred just minutes after the race began when the 24-year-old Honda rider's bike veered across the track and into the path of riders Colin Edwards and Valentino Rossi.
Simoncelli had his helmet knocked off in the ensuing collision, which occurred on turn 11.
MotoGP later announced Simoncelli's death in a one-line statement on its website. "Marco Simoncelli succumbed to injuries sustained in Malaysia," it said.
Motor sports have seen a nightmare stretch recently and Simoncelli's death looked certain to throw open more questions over safety.
Last weekend, 2010 MotoGP champ Jorge Lorenzo crashed during warm-ups in Australia, severing a finger, while two-time Indianapolis 500 winner Dan Wheldon died in a 15-car crash in Las Vegas in Indy Car. The race at Malaysia's Sepang track was immediately red-flagged following the crash and organisers later announced it had been cancelled.
Edwards also fell but escaped serious injury, while Rossi was able to return to the pits. Although there is a final race in Spain still to come, Australia's Casey Stoner has already secured the 2011 championship with his win last weekend in the Australian Grand Prix.
Published 23 October 2011, 10:32 IST