The Honda rider, who was comfortably fastest on day one, flew to a new benchmark of 1m59.926s, leaving him the only rider to crack the 2m00s barrier.
Last year's pole time at the Malaysian track was a 2m00.011s, set by Marquez's works team-mate Dani Pedrosa.
The Spaniard was Marquez's closest challenger, but was still more than four tenths of a second off.
Stefan Bradl meanwhile ensured a top three lockout for Honda, going third fastest - just three thousandths of a second down on Pedrosa - for the LCR satellite squad.
Yamaha's works duo Valentino Rossi and Jorge Lorenzo wound up fourth and sixth respectively, both men finishing within 0.7s of Marquez.
They were split by Aleix Espargaro, who continued Forward Racing's excellent start to its new programme with Yamaha-based Open class machinery.
Bradley Smith backed up his works counterparts by putting his satellite Tech 3 Yamaha seventh, three hundredths of a second down on two-time champion Lorenzo.
As was the case on the first day, none of the factory Ducati riders made it into the top 10, although the Italian marque was represented as Andrea Iannone put his satellite Pramac machine eighth overall.
Gresini Honda rider Alvaro Bautista and the second Tech 3 Yamaha of 2013 Moto2 champion Pol Espargaro rounded out the top 10, ahead of Ducati duo Andrea Dovizioso and Cal Crutchlow.
Nicky Hayden finished best of the rest for his new Aspar team, one of three outfits using Honda's production racer this season.
Wednesday testing times
1. MARQUEZ, Marc Repsol Honda Team 01:59.9
2. PEDROSA, Dani Repsol Honda Team 02:00.3 +0.41
3. BRADL, Stefan LCR Honda MotoGP 02:00.3 +0.413
4. ROSSI, Valentino Yamaha Factory Racing 02:00.5 +0.538
5. ESPARGARO, Aleix NGM Mobile Forward Racing 02:00.5 +0.621
6. LORENZO, Jorge Yamaha Factory Racing 02:00.6 +0.647
7. SMITH, Bradley Monster Yamaha Tech 3 02:00.6 +0.677
8. IANNONE, Andrea Pramac Racing 02:00.9 +0.929
9. BAUTISTA, Alvaro GO&FUN Honda Gresini 02:00.9 +0.971
10. ESPARGARO, Pol Monster Yamaha Tech 3 02:01.1 +1.135
11. DOVIZIOSO, Andrea Ducati Team 02:01.1 +1.22
12. CRUTCHLOW, Cal Ducati Team 02:01.4 +1.47
13. PIRRO, Michele Ducati Test Team 02:02.2 +2.251
14. HAYDEN, Nicky Drive M7 Aspar 02:02.3 +2.361
15. EDWARDS, Colin NGM Mobile Forward Racing 02:02.5 +2.619
16. HERNANDEZ, Yonny Energy T.I. Pramac Racing 02:02.7 +2.749
17. AKIYOSHI, Kosuke HRC Test Team 02:02.7 +2.766
18. AOYAMA, Hiroshi Drive M7 Aspar 02:02.8 +2.899
19. NAKASUGA, Katsuyuki Yamaha Factory Test Team 02:03.0 +3.044
20. DE PUNIET, Randy Suzuki Test Team 02:03.1 +3.138
21. REDDING, Scott GO&FUN Honda Gresini 02:03.1 +3.191
22. LAVERTY, Michael Paul Bird Motorsport 02:03.5 +3.602
23. BARBERA, Hector Avintia Racing 02:04.6 +4.625
24. PARKES, Broc Paul Bird Motorport 02:04.6 +4.693
25. ABRAHAM, Karel Cardion AB Motoracing 02:05.3 +5.335
26. DI MEGLIO, Mike Avintia Racing 02:05.4 +5.429