The Spaniard finished a distant second, while Casey Stoner - riding with damaged ligaments and a fractured right ankle - was denied a podium after a long fight with Andrea Dovizioso.
The Spaniard's only realistic rival was Yamaha's Ben Spies, who led in the early laps but then suffered a blown engine – the latest in a string of misfortunes for the Texan – while running second.
That left Pedrosa to cruise to victory, with the Spaniard's ability to up his pace and lap beyond the capability of the rest of the MotoGP field turning the race into something of a procession out front.
A new lap record underlined his complete control at the halfway mark, and while he suffered a moment at Turn 2 one lap later he was still able to edge away from Lorenzo, eventually cruising home to a 10 second victory margin.
"It was a good weekend. I think the bike was working well. We were spinning all of practice, but we had a good feeling. So today for the race I was confident," Pedrosa said.
"When I shifted again to first, the bike had a good kick on me and yeah, I almost lost control," Pedrosa said. "But I kept the bike on the track. I lost one second on that lap."
With Spies out, the fight for the final podium spot boiled down to Tech 3 Yamaha's Andrea Dovizioso and Stoner.
The Australian had previously come through from seventh, passing the satellite Hondas of Alvaro Bautista (Gresini) and Stefan Bradl (LCR) before also picking off Dovizioso.
The Italian kept him honest however and seven laps from the end moved back in front, before eventually breaking free of the Australian as the latter faded in the final few laps.
Stoner now trails Lorenzo by 36 points in the championship.
Bautista beat Bradl to sixth, while a long way down the road – and only slightly ahead of the lead CRT riders – Valentino Rossi came home a lonely seventh.
Cal Crutchlow had held the position until crashing out at Turn 4 early on, the first time this year he has failed to score points.
Avintia's Yonny Hernandez and Aspar's Aleix Espargaro were set to match the highest CRT finish of 2012 as they squabbled for eighth, but their fight was demoted to one for ninth late on as Karel Abraham (Cardion Ducati) came through.
Hernandez eventually triumphed in the battle, with Espargaro therefore completing the top 10.