Peyton Manning threw for 318 yards and four touchdown passes, with his third breaking Brett Favre's all-time mark.
Two of them went to Demaryius Thomas, whose eight catches went for 171 yards.
Ronnie Hillman posted 103 yards from scrimmage and two rushing touchdowns, including a 37-yarder (video), the longest play of his career (and no fumbles!). He'd entered the game with just two career touchdowns, one in each of his first two seasons.
Peyton led Denver to six touchdowns in eight possessions before being wisely yanked by John Fox early in the fourth quarter. It was of particular importance to rest starters on this night, with the shortest of turnarounds leading to a huge matchup with San Diego (5-2) on Thursday.
Manning and the offense were of course the main story, but this was the team's first clicking-on-all-cylinders game of the year.
Denver held San Francisco to 310 yards of offense (many of them in garbage time) and 3/13 on third downs.
Six of the Niners' 11 possessions went for 10 or fewer yards, four of them for zero yards or a loss.
DeMarcus Ware sacked Colin Kaepernick three times, Von Miller took him down twice, and Aqib Talib intercepted him once (video).
That defense and a missed 48-yard FG by Phil Dawson provided the Broncos with prime field position for its first two drives.
Emmanuel Sanders finally collected his first Denver touchdown on Manning's initial scoring pass of the night (video).
On his second, Wes Welker dove for the near left pylon for a 39-yard score (video).
Following a rare fruitless possession, Manning broke Favre's record with an eight-yard pass to Demaryius Thomas (video).
And after Talib's pick set Denver up at the plus-40, Peyton hit Demaryius with a picturesque first-down throw (video).
Hillman capped the next two possessions with touchdowns - his second from one yard out (video) - and Manning's night was over.
The Broncos are now alone in first place atop the AFCW, with a chance to stretch out to a 1.5-game lead over the Chargers with a win on Thursday.
Only Dallas (6-1) has a better record, while Philly and Arizona are also 5-1.
Here's what Peyton had to say.