The Honda rider knocked Jorge Lorenzo off the top spot with 11 minutes remaining with a 2m04.140s lap, and then improved his own pace as the chequered flag came out to end the session on 2m03.941s.
Lorenzo was 0.416s slower than the world champion, with his Yamaha team-mate Ben Spies snatching third spot on his final lap. Andrea Dovizioso, Alvaro Bautista and Dani Pedrosa completed the top six for the Tech-3 Yamaha, Gresini Honda and factory Honda teams respectively.
The Ducatis of Nicky Hayden and Valentino Rossi were seventh and ninth - split by the Pramac-run GP12 of Hector Barbera.
Rossi, the early pace-setter in dry conditions, had a brief off into the gravel at Club, but was able to negotiate his way into the pitlane without falling off.
Randy de Puniet was the best of the CRT riders in 10th on his Aspar Aprilia while Britain's James Ellison was 13th on his similar, Paul Bird Motorsport-run machine.
The biggest incident of the session came when British hero Cal Crutchlow crashed after losing the front of his Tech-3 Yamaha at Chapel. After being flung to the ground, he was taken to the medical centre with a suspected broken ankle.
LCR Honda's Stefan Bradl was also taken to the medical centre after a crash, while Yonny Hernandez also crashed but walked away and was able to resume the session on his spare bike.