The drama began when Karel Abraham stalled his Ducati just before the lights went out, forcing another pre-race routine and warm-up lap.
The Spaniard's front tyre warmer could not be removed for the restart so the Repsol Honda had to wheeled off the grid.
The wheel then unlocked, allowing the cover to be removed and for him to start from the back, while Abraham had to start from the pitlane with a problem of his own.
As Pedrosa sought to cut through the field on the opening lap, Hector Barbera collided with him on a corner and both crashed out.
Valentino Rossi delighted the crowd with second place on what is effectively his home race, while Alvaro Bautista held off Andrea Dovizioso by 3/1000ths of a second to finish on the podium after a brilliant ride.
Lorenzo took a lights-to-flag victory that saw him build a steady lead throughout on his factory Yamaha, finishing five seconds ahead of Rossi.
The Italian legend was all alone on the Ducati by the finish, with his main work coming off the line as he charged straight up to second from his qualifying position of sixth.
Bautista was seventh after the first lap, having dropped from fifth - or effectively fourth - on the grid, but would singled-handedly provide the majority of the entertainment with a fantastic performance from there.
Briton Cal Crutchlow, looking to become the first British rider since Ron Haslam in 1987 to score back-to-back podium finishes in the top class, gave him one spot back when he crashed out on lap four of the 27-lap race. It had been reduced by one lap as a result of the early farce.
San Carlo Gresini Honda rider Bautista quickly overtook the factory Yamaha of Spies for fifth and worked on the large gap to Dovizioso, catching him with 12 laps remaining and executing a smooth pass two laps later.
Stefan Bradl, wringing performance out of the LCR Honda, was next - and the flying Bautista eased past him and into the podium places three laps further on. Bradl would eventually finish sixth behind Dovizioso and Spies after dropping both places in successive corners on lap 23.
The battle was not yet won, however, with Dovizioso finding something extra from the Tech 3 Yamaha to close on him. The Italian pulled alongside on the finishing straight and was only denied third spot by the timing system with the riders level to the naked eye.
Briton Jonathan Rea, fifth in the World Superbike standings this season, took an impressive eighth spot behind Nicky Hayden having finished ninth in qualifying on the grand prix debut for Repsol Honda.