Fiat Yamaha has now won the 2010 Teams' title to add to the Riders' crown and are 39 points clear of Honda in the Constructors' standings.
Starting from the outside of the front row, Spies had briefly held second place through turn one, but lost ground after Lorenzo cut across his nose into the following left hander.
Riding at a track he made his victorious WSBK debut at in 2009, Spies spent most of the race fighting fellow rookie Marco Simoncelli for fifth position, which Spies finally took from the Gresini Honda rider with five laps to go.
Spies, who has taken two podiums this year for Monster Yamaha Tech 3, has now wrapped up the 2010 MotoGP Rookie of the Year title. Team-mate Colin Edwards was seventh, as Pramac Ducati's Aleix Espargaro, Simoncelli's team-mate Marco Melandri and Honda LCR's Randy de Puniet completed the top ten.
Mika Kallio, riding in what looks to be his last MotoGP event before being replaced by Carlos Checa for the last two rounds, was eleventh. Alvaro Bautista took twelfth at what is traditionally Suzuki's worst circuit.
No Repsol Honda rider finished the race as Andrea Dovizioso, having dropped to last place, pitted and then retired with some kind of technical problem.
Team-mate and former 2010 title contender Dani Pedrosa withdrew from the race due to a lack of strength from the collarbone he fractured in Japan on October 1.
Rizla Suzuki's Loris Capirossi was also absent after straining the Adductor muscle at the top of his left thigh when he crashed on Saturday.
Australia was the last of three flyaway events, in three consecutive weekends. The next round, the penultimate event of the year, will be held at Estoril, Portugal, on October 31.
Australian Grand Prix:
10. de Puniet