Manning, who last week surpassed New England quarterback Tom Brady's single season record of 50 touchdown passes, set the standard for most passing yards in a season, and the Broncos established a league high for points scored.
Manning's 63-yard touchdown pass to DeMaryius Thomas gave the Broncos 595 points this season, breaking the NFL's record of 589 set six years earlier by the Patriots.
The Denver quarterback's second scoring connection to Thomas, this time a five-yard strike in the final seconds of the first half, gave Manning 5,477 passing yards on the season to surpass the 5,476 yards put up by New Orleans Saints quarterback Drew Brees in 2011.
Manning threw four touchdown passes in the first half against Oakland to give him 55 on the season.
The AFC West champion Broncos (12-3) led 31-0 at intermission and were poised to clinch homefield advantage throughout the playoffs with a victory.