Reigning MotoGP champion Casey Stoner was rushed off to hospital with what was later confirmed as torn right ankle ligaments after he came off his bike on the bumpy and slippery American circuit just minutes into the session.
Stoner had a ferocious high-side at turn 13 and was thrown through the air and landed heavily, feet first, before tumbling through the gravel. His Honda had a separate series of dramatic flips.
The Australian is currently third in the world championship in what will be his final MotoGP season before retiring, 32 points behind leader Jorge Lorenzo with eight grands prix remaining.
Ben Spies also crashed heavily in the second half of the hour-long qualifying but was able to walk away, while Nicky Hayden's horrifying smash in the closing minutes led to him being taken away from the track in an ambulance - though he was sitting up and talking - after his bike, too, buckled away from beneath him after hitting a bump.
The session was red flagged after Hayden's crash, restarting with eight minutes left to allow Pedrosa to pull out a best lap of 1:38.813.
Jorge Lorenzo pushed Pedrosa hard in the closing stages but was a tenth slower to start second on the grid, with Andrea Dovizioso third and Ben Spies fourth - though the American might well have been on pole had he not crashed, as he was half a second up going in to turn 13.
Stefan Bradl impressed to be fifth quickest while Stoner, despite having completed just three early laps, was still quick enough to start sixth should he be well enough to race on Sunday.
In Moto3 qualifying Sandro Cortese took pole with a lap of 1:48.545, less than a tenth of a second faster than Britain's Danny Kent. Maverick Vinales was third fastest.