Manning completed 30-of-38 passes for 338 yards in his fourth game since coming to the Broncos as a free agent in the off-season, sparking Denver to 27 unanswered points.
Star running back Darren McFadden was limited to 34 yards on 13 carries for Oakland (1-3).
Carson Palmer passed for 202 yards on 19-of-34 efficiency in the loss.
Puzzle-maker slips 'Murdoch Is Evil' into Rupert Murdoch's Sunday Telegraph
Reindeer recovered after escaping from Santa during lighting ceremony