Stoner, chasing a US MotoGP double having also triumphed in Laguna Seca last month, will start from the top slot for the seventh time this season looking to build on his 32 point cushion over Spaniard Jorge Lorenzo at the top of the championship standings.
The Australian guided his Honda around the 2.61 mile layout, which uses part of the Indianapolis Motor Speedway's oval, in a time of one minute, 38.850 seconds to finish ahead of American hope Ben Spies on a sweltering hot day at the famed Brickyard.
World champion Lorenzo was third quickest followed by compatriot and last year's Indy winner Dani Pedrosa.
Leading qualifying times on Saturday at the 2.621-mile Indianapolis Motor Speedway road course:
Moto GP
1. Casey Stoner (AUS/Honda) 1min 38.850secs. 2. Ben Spies (USA/Yamaha) at 0.523, 3. Jorge Lorenzo (ESP/Yamaha) at 0.779, 4. Dani Pedrosa (ESP/Honda) at 1.097, 5. Andrea Dovizioso (ITA/Honda) at 1.174, 6. Colin Edwards (USA/Yamaha) at 1.248, 7. Marco Simoncelli (ITA/Honda) at 1.354, 8. Nicky Hayden (USA/Ducati) at 1.394. 9. Alvaro Bautista (ESP/Suzuki) at 1.483. 120. Hector Barbera (ESP/Ducati) at 1.510.
125cc
1. Nicolas Terol (ESP/Aprilia) 1:48.199, 2. Sandro Cortese (GER/Aprilia) at .720, 3. Johann Zarco (FRA/Derbi) at .740, 4. Maverick Vinales (ESP/Aprilia) at .792, 5. Danny Kent (GBR/Aprilia) at 1.057.