With the victory, Pittsburgh's fifth straight, the Steelers set up a showdown with Cincinnati for first place in the AFC North. The Steelers (6-2) host the Bengals (6-2) Sunday.
Denver, meanwhile, fell to 6-2 after a 6-0 start and is just one game ahead of San Diego in the AFC West.
Ben Roethlisberger continued his strong play for the Steelers, rebounding from a 3-for-6 start to finish 21 of 29 for 233 yards, 3 touchdowns and an interception. Rashard Mendenhall had his second 100-yard game of the season, gaining 155 yards on 22 carries.
Using a quick passing attack right out of the playbook of the New England Patriots, where first-year head coach Josh McDaniels was an offensive coordinator and quarterbacks coach, the Broncos found success in the first half. Quarterback Kyle Orton was 16 of 21 for 163 yards in the first two quarters, as Denver outgained Pittsburgh, 183-54.
While Orton was connecting on the majority of his short passes, leading the Broncos on a field goal drive to open the game, he also made a critical error early in the second quarter.
On third down from his own 31, Orton threw over the middle to running back Knowshon Moreno. As Orton released the ball, Moreno ran into umpire Garth Felice. The ball sailed into the arms of safety Tyrone Carter.
Starting in place of Ryan Clark, Carter returned the interception 48 yards for a touchdown and a 7-3 lead.
The Broncos drove to the Pittsburgh 39 on their next possession, but Orton's third-down pass to Jabar Gaffney was broken up by William Gay. Coach Josh McDaniels decided to go for it on fourth down,but guard Ben Hamilton was penalized for holding Pittsburgh linebacker James Harrison on the play, and the Broncos punted.
The Broncos took the lead early in the second half. Roethlisberger was sacked by Ken Peterson, who forced a fumble. Rookie linebacker Robert Ayers scooped it up and returned it 54 yards for a touchdown.
The Steelers stayed in the no-huddle and again quickly moved into Denver territory, with Mendenhall breaking off a 24-yard run and Roethlisberger connecting with Santonio Holmes for a 35-yard gain to the Denver 4. Roethlisberger then tossed a 4-yard TD pass to Hines Ward to give the Steelers a 14-10 lead.
An interception by Troy Polamalu with 8:31 remaining gave the Steelers the ball at the Denver 25 and Roethlisberger made the Broncos pay with a 25-yard TD pass to rookie wide receiver Mike Wallace to put the Steelers comfortably ahead, 21-10. Ward finished the scoring with a 3-yard reception from Roethlisberger.