The defending champion won the season opener in Qatar last month and he repeated the feat in Austin this time around, never looking in trouble after starting on pole.
The Spaniard led throughout, only suffering a slight wobble at the final corner, before recovering to finish 4.124 seconds in front of Repsol Honda team-mate Dani Pedrosa.
Ducati's Andrea Dovizioso (+20.976secs) made up the podium, while team-mate Cal Crutchlow crashed out midway through the race and suffered a broken right hand.
Six-time champion Valentino Rossi, second in Qatar, struggled throughout and finished in eighth, over 45 seconds off the pace.
Jorge Lorenzo, who crashed out in last month's season-opening race, jump-started from fifth on the grid and after a penalty, recovered to finish 10th.
Marquez now sits 14 points clear of Pedrosa at the top of the standings, with Rossi dropping down to third overall, a further eight points adrift.
The defending champion was in jovial mood afterwards, joking that his final-corner blip was to liven up what had been a "boring" race.
"I'm so happy for this victory," he told BT Sport. "It was too quiet, but I did something at the end!
"I'm very happy, the start was good and that's important. The race I think was even for me a little bit boring but the 25 points are important."
Ducati team boss Gigi Dall'igna, meanwhile, confirmed Crutchlow's injury and said the Brit may be unable to race in Argentina in two weeks' time.
"I didn't speak with him but for sure he has a broken hand and that's a problem for the next race," he said.
Dovizioso was thrilled with his third-placed finish, after a difficult 2013 in which he failed to record a single top-three result.
"It's a really special feeling because we struggled a lot but we keep pushing and we keep working," he said.
"We didn't have the pace to make a podium (before) but we always tried. I was focused and didn't make a mistake.
"I was really consistent and to get a podium at the end is an amazing feeling."