Marquez (Repsol Honda Team) dropped back from pole position on the first lap but showed his class to prevail in front of 80,000 fans in the blistering heat at Sepang.
The 21-year-old Spaniard’s triumph equalled Mick Doohan’s record of most premier-class wins in a single campaign, and secured the constructors’ title for Honda.
Marquez – already guaranteed the title – enhanced his credentials still further at the Sepang International Circuit on Saturday by becoming the first rider to secure 13 poles in a single season.
The weekend continued in a similar vein as he drew level with the mark set by Australia’s five-time world champion Doohan.
The victory was Marquez’s first since his triumph at Silverstone in August, while Movistar Yamaha MotoGp riders Rossi and Lorenzo will battle it out for second place in the final race of the year in Valencia after Dani Pedrosa (Repsol Honda) crashed out.
Despite veering into the gravel, Marquez was quickest in the warm-up at Sepang, but it was Pedrosa and Lorenzo who made strong starts.
Marquez slipped to sixth after running wide as Lorenzo surged into the lead before a series of riders saw their races come to premature ends – Aleix Espargaro and Alvaro Bautista forced out after a crash at turn one.
A mechanical fault signalled the end of Cal Crutchlow’s race and Pedrosa then retired as he crashed for a second time, having recovered to 11th following a failed bid to challenge Lorenzo at turn 15.
At the front, Rossi threatened to make it back-to-back victories as he led Lorenzo and Marquez, but the two-time world champion recovered to claim top spot by 2.445 seconds.
Lorenzo was 3.508secs further back, and Marquez could now cap a memorable season in Valencia – a win in his homeland would take him past Doohan’s record.
Just 12 points separate Rossi and Lorenzo, with the battle for second going down to the wire.