Pedrosa's accident had promoted world championship leader Lorenzo into a short-lived podium position - just in front of Valentino Rossi and Andrea Dovizioso.
Winner at Le Mans for the past two years, Lorenzo had struggled to match the factory Hondas in practice - then suffered a fiery fall in warm-up. The two Italians smelt blood and finally surged past Lorenzo with four laps to go, with Simoncelli heading for pit lane soon after.
Dovizioso then made it a Repsol one-two by passing Rossi with three laps remaining.
Despite a tough start to his Ducati career, Rossi showed no signs of backing off and confirming a first ever Desmosedici rostrum and instead pushed Dovizioso right to the flag.
Stoner crossed the line a huge 14.2sec ahead of Dovizioso and has now moved ahead of Pedrosa into second in the standings, 12 points behind Lorenzo, whose fourth place on Sunday ended a seven-race run of rostrums.
Spies was ten-seconds behind his team-mate in sixth, while both satellite Tech 3 riders - Cal Crutchlow and Colin Edwards - crashed from the team's home race. Edwards returned to finish 13th and last, while Crutchlow was forced to retire after also attempting to rejoin.
Rossi's team-mate Nicky Hayden recorded seventh place, Simoncelli's team-mate Hiroshi Aoyama eighth and Aspar Ducati Hector Barbera ninth. Barbera just held off Karel Abraham (Cardion AB), Toni Elias (Honda LCR) and Alvaro Bautista (Rizla Suzuki) at the flag.
Randy de Puniet, the only French rider in MotoGP, was involved in a controversial clash with Stoner in morning warm-up - for which the Australian was fined (see separate story).
de Puniet was the first of the fallers in the race, hitting the deck on lap two, team-mate Loris Capirossi later joined him on the sidelines.
Round five of the 2011 world championship takes place at Catalunya on June 5.
French Grand Prix: