Two-time World Champion Jorge Lorenzo put on a masterclass in Mugello, winning his third consecutive race to take out the Italian Grand Prix ahead of Ducati's Andrea Iannone and Yamaha's Valentino Rossi.
The Yamaha of Lorenzo was too quick for the rest of the field, as the Spaniard took the lead within the first two laps and did not relinquish it until he crossed the chequered flags.
Lorenzo now trails Yamaha's Valentino Rossi by only six points in the 2015 World Championship, with the next race taking place in Lorenzo's home country of Spain.
Ducati rider Andrea Iannone finished the race in second place after starting on pole position for the first time of his young career, fighting through the pain of a shoulder injury to finish ahead of countryman Valentino Rossi in third.
Rossi started the race in eighth position, but worked his way through the pack methodically to set his sights on a podium position in the final ten laps, as the Ducati of Andrea Dovizioso retired from the race, pushing Rossi into fifth.
For Marquez - it was a race of two halves, as a horror qualifying session relegated Marquez to 13th place the grid, but a brilliant start saw the Spaniard roar into 3rd place after the opening lap, where he began to challenge the leaders.
Things were looking up for the Honda of Marquez, as a position on the podium looked to be in his sights when he overtook Iannone for second place - but disaster struck with six laps remaining, as Marquez slid off his bike and out of the race, much to the delight of the partisan Italian crowd.
Rossi then set his sights on Marquez's team-mate Dani Pedrosa - and on the same lap, the Italian moved into third position, sending the crowd into a frenzy.
Pedrosa finished the race in fourth place, ahead of Yamaha's Bradley Smith and Pol Espargaro.
Suzuki's Maverick Vinales crossed the line in seventh in front of Italians Michele Pirro and Danilo Pettrucci of Ducati.
Yonny Hernandez's finished tenth, giving Ducati four bikes in the top ten, with Hector Barbera also registering points in 13th.
Australian Jack Miller failed to finish after completing only two laps.
2015 World Championship Top Ten
1. 118 Points (+16) - Valentino Rossi (Yamaha)
2. 112 Points (+25) - Jorge Lorenzo (Yamaha)
3. 83 Points (DNF) - Andrea Dovizioso (Ducati)
4. 81 Points (+20)- Andrea Iannone (Ducati)
5. 69 Points (DNF)- Marc Marquez (Honda)
6. 57 Points (+11)- Bradley Smith (Yamaha)
7. 47 Points (DNF)- Cal Crutchlow (Honda)
8. 45 Points (+10)- Pol Espargardo (Yamaha)
9. 36 Points (+9) - Maverick Vinales (Suzuki)
10. 32 Points (+7) - Danilo Petrucci (Ducati)