Italy's seven-times world champion Valentino Rossi burst into fourth place on the final lap.
Marquez's win, his third victory in a row, completes his sweep of the races in the United States following his wins at Laguna Seca and Austin.
"Maybe I should make America my next country, I've won the three races here... I love it," joked Marquez after extending his lead at the top of the standings to 21 points from Pedrosa (167) and reigning world champion Lorenzo (153).
Marquez topped every session he took part in during the weekend and started on pole for the 27 lap race.
After making a poor start the 20-year-old fought his way into the lead overtaking Lorenzo on the ninth lap and Pedrosa four laps later.
Pedrosa looked like he would have to settle for third place but powered ahead of Lorenzo at the start of the penultimate lap.
Pedrosa and Lorenzo, both coming back from injuries, gained their first podium finishes since the Catalan Grand Prix in Barcelona two months ago.
Rossi's late burst saw him overtake Cal Crutchlow and Alvaro Bautista on the final lap to claim fourth.
(Reporting By Simon Evans in Miami, editing by Pritha Sarkar)
