Having already proved unstoppable in pre-season testing at the Texan venue and the Friday morning session, it was little surprise when Marquez led the way again in practice two.
He briefly put himself 1.8 seconds clear of his rivals before his Honda team-mate Dani Pedrosa closed the gap to more respectable levels.
Marquez ended his day with the fastest laps of all: a 2:05.031s and then a second tour just 0.016s slower.
That was over three seconds quicker than in the morning, when cold and windy conditions added to the challenge of the dusty surface and the unfamiliar track.
Second-placed Pedrosa was 0.554s adrift.
Stefan Bradl made it an all-Honda top three as he jumped to third for LCR in the final moments. The German had spent a while on top early on.
He was 1.1s off Marquez's pace, but still half a second clear of the top non-Honda rider, which was Yamaha's Jorge Lorenzo.
His team-mate Valentino Rossi completed the top five, followed by Tech 3's Cal Crutchlow - the quickest of the riders who had not tested at Austin in March.
Andrea Dovizioso lost time when he had to park his primary Ducati at the far end of the track with a mechanical problem. The Italian still managed seventh place.
Nicky Hayden was the quickest of the home riders on the second Ducati, taking ninth behind Alvaro Bautista, and just ahead of Ben Spies.
Aleix Espargaro set the CRT pace in 11th, a second clear of nearest rival Yonny Hernandez.
Espargaro's Aspar team-mate Randy de Puniet had a wild crash in the penultimate complex of corners, but avoided injury despite some scary moments as he balanced on his out-of-control Aprilia on its way to the ground.