The rookie, who dominated all practice sessions and started from pole position, came through from third position early on to pass both his team-mate Dani Pedrosa and defending World Champion Jorge Lorenzo en route to a victory by 3.5s.
It was a Repsol Honda one-two with Pedrosa managing to get through on Lorenzo in the closing stages, but by that stage victory belonged to Márquez who collected his third consecutive victory after his triumphs in the two previous rounds in Germany and at Laguna Seca.
“I didn't make such a good start but I knew before the race that the most important part was going to be the end of the race,” said Márquez – who has won all three Grands Prix held in the USA this year – post-race.
“In the first 10 laps I just tried to follow Dani and Jorge, and to save the tyres, and then when I felt ready – when the fuel load went down a little bit – I tried to attack.
“In the beginning Jorge was able to follow me, but then I tried to push a bit more. I felt so good with the bike and I opened a gap that meant in the end I was able to enjoy sliding the bike and that was really great!
The 25 points are important and I feel great here in the USA. I have won the three races here so that's important.
“Now we got back to Europe and we'll try to continue in that way!”
A great scrap for fourth between Cal Crutchlow, Valentino Rossi and Álvaro Bautista went down to the very finish with Rossi coming out on top after a daring overtake on the final lap.
When the race got underway it was Lorenzo who got the best start, firing his Yamaha into first place and leading for the early part. Pedrosa and Márquez tucked into second and third respectively, as a waiting game unfolded with the trio tightly bound.
Márquez picked off Pedrosa with a move around the outside on lap nine before making his pass on Lorenzo on lap 13 – the halfway stage – and built his lead from there.
Lorenzo and Pedrosa remained close together as Márquez pulled away, and desperate not to allow his younger team-mate too much of a boost at the top of the Championship Pedrosa edged past Lorenzo going into Turn 1 with just two laps remaining to take second position, which he held to the finish.
The result means Márquez now leads by 21 points, with Pedrosa second and Lorenzo 35 points adrift of top spot in third.
Aside from the battle at the front there were trades all the way through the field. Rossi recovered from as low as seventh and more than five seconds off fourth place to take it with his dash up the inside of Crutchlow at the end, while Stefan Bradl placed seventh after finishing on the podium at Laguna Seca.
Bradley Smith nipped in to take eighth as Ducati team-mates Nicky Hayden and Andrea Dovizioso clashed in the final corner on the last lap and ran off, finally crossing the line in ninth and tenth respectively.
The Championship now heads straight to Brno for the Czech Republic Grand Prix – Round 11 of the season.