It was Manning who found his form first as he opened the second period by firing a short pass straight to Sanders to hand the lead to the Broncos.
The Chargers responded to the setback impressively as Rivers clicked into top gear to spot the run of Keenan Allen, whose touchdown allowed the visitors to level the scores.
However, Manning would have the final say before the half-time interval as he finished an eight-play drive with a 31-yard pass into the waiting hands of Sanders in the endzone.
The Broncos took control of the contest early in the third quarter as Sanders collected another pass from Manning to complete his hat-trick of touchdowns, before Juwan Thompson capitalised on a gap in the San Diego defense by rushing two yards to make it 28-7.
Rivers drove the Chargers forward once again with a long drive which resulted in the visiting QB reducing the deficit with a short touchdown pass to Antonio Gates.
Thompson displayed his strength once again by powering over from a yard out in the fourth quarter to restore his side's 21-point advantage, but the Chargers kept alive their slim hopes when Gates drifted to the left of the endzone to get his hands on another inch-perfect pass from Rivers.
There would be no late comeback from the Chargers, though, with Brandon McManus missing a field goal to give Denver an even bigger win in the closing stages.