Keen to make a break, Rea attempted to wrest the lead from Sykes on lap 15 with a pass through turn one, but the Kawasaki rider kept it cool to simply re-pass at turn two.
With the group whittled down to six riders, Melandri only began to make his move with five laps remaining, overtaking Laverty, Baz, Checa and Rea in consecutive laps to be running second with three laps to go.
With momentum on his side, Melandri simply nosed his BMW ahead for the first time on lap 19, demoting Sykes into the clutches of Rea. However, their battle would come to a sudden halt shortly afterwards when Sykes ran wide at turn 11, prompting Rea to attempt to capitalise by diving inside.
However, Sykes would simply cut back onto the racing line, making solid contact with Rea that would send the Honda rider into a dramatic high-side and out of the race.
While Sykes was able to stay upright, it was the end of his victory challenge, with Melandri taking advantage of the breathing space to cross the line almost two seconds ahead of the Kawasaki rider.
With Rea out and Checa delayed by the Honda somersaulting in front of him, Baz grabbed his moment to complete the podium in only his fifth WSBK event, the result in turn marking a successful double rostrum result for the Kawasaki team.
Checa recovered to fourth by setting the fastest lap on the final revolution, while Laverty settled for fifth having never been able to get stuck into the lead battle.
A flurry of quick laps mid-race would see Biaggi come through into sixth place to limit the damage to his championship lead, ahead of Haslam and Michel Fabrizio.
Berger held on for a still respectable ninth place finish, ahead of team-mate Jakub Smrz, while Chaz Davies completed a fairly lonely race in 11th position.
More than a minute behind the leaders, Alex Polita and Norino Brignola finished ahead of better fancied rivals for 12th and 13th, while Leon Camier and John Hopkins picked up the final points for FIXI Crescent Suzuki.