The record-shattering effort came in the first half against the Oakland Raiders, giving the visiting Broncos a 31-0 half-time lead.
Manning, the Broncos' 37-year-old quarterback, threw for 266 yards and four touchdowns in the first half against the Raiders.
His first-half yardage total was exactly what he needed to break the former one-season record of 5,476 passing yards set by Drew Brees of New Orleans in 2011.
Manning set the yardage mark on a 5-yard touchdown pass to Demaryius Thomas with 13 seconds remaining in the second quarter to give him 5,477 yards on the season.
That was Manning's fourth touchdown pass of the game, giving him 55 touchdown tosses for the season. Last week, he broke the old one-season touchdown pass record of 50 set by New England's Tom Brady in 2007.
The 2007 New England squad had also set the NFL one-season scoring record of 589 points, but the Broncos entered their final regular-season contest needing only 18 points to break that record.
By halftime, Denver had pushed the record to 603 points, the record falling on Manning's 63-yard touchdown pass to Thomas in the second quarter.