With the teams battling for AFC playoff positioning, Manning looks to help guide Denver to its ninth straight victory Sunday while winning his ninth consecutive start against the Ravens, whose offense is now being run by one of Manning's mentors.
Manning has been stellar in his first season with Denver, throwing for an AFC-best 30 touchdowns with a 104.0 passer rating that ranks fourth in the NFL while guiding the Broncos (10-3) to the AFC West title.
He finished 26 of 36 for 310 yards and a touchdown Dec. 6 in a 26-13 win at Oakland to give the team its longest winning streak since the 1998 John Elway-led Broncos won their first 13 games en route to their second straight Super Bowl.
Denver has dropped each of its five trips to Baltimore - including the last two by a combined 37 points - but Manning may be who it needs to end that streak.
Manning has won each of his last eight starts versus the Ravens, including two postseason victories. He led Indianapolis to a win in the divisional playoffs the last time he faced them Jan. 16, 2010.
"I can't speak to the past,'' said Manning, who has won four times in Baltimore during that stretch. "All I know is, we're going on the road, playing an excellent team.''
The Broncos are one game ahead of the Ravens (9-4) for the No. 3 seed in the AFC playoff race, and coach John Fox believes his team will have a tough time extending its winning streak.
"This will be a playoff-type game," Fox said. "You're talking about a team that's been in the playoffs four straight years, I think coach (John) Harbaugh's done a tremendous job. They've got excellent staff, excellent football team, they know how to win and part of that is being tough at home. They've only lost one game there this year (out of six)."
Harbaugh said his team knows what's at stake.
"It's a big game - we don't really need an incentive," Harbaugh said. "The fact that us and Denver are both kind of in the mix for seeding and for division championships and those kind of things, that makes it really interesting. This is a game that everybody should be excited about."
The Ravens, though, enter on a two-game skid after falling 31-28 in overtime at Washington last Sunday. They also lost 23-20 on Dec. 2 when Pittsburgh kicked a field goal as time expired to end Baltimore's 16-game home winning streak.
The Ravens' last home loss to anyone other than the Steelers was to Manning and the Colts on Nov. 22, 2009.
Indianapolis' coach that day will now be calling plays for Baltimore after Harbaugh on Monday made what he called one of the toughest decisions of his career. With four turnovers in the past two weeks and the offense sputtering at 344.4 yards per game - 18th in the NFL - the Ravens fired offensive coordinator Cam Cameron and replaced him with Jim Caldwell.
Caldwell has served as Baltimore's quarterbacks coach this season after being fired by Indianapolis in January.
"The little time that he's been here, we've had a great working relationship," said Joe Flacco, who went 16 of 21 for 182 yards and three touchdowns last week.
That's not surprising given Caldwell's relationship with Manning while serving as his quarterbacks coach for seven seasons and head coach for three with the Colts.
"I felt like he really took my game to another level," Manning said. "He's also a tremendous mentor and friend to me."
While the Ravens' offense gets accustomed to a new leader, the defense has plenty of holes to fill.
Suggs (bicep) may be back this week after sitting out against Washington, while there's a chance Lewis (triceps) could play for the first time since Week 6.
Defensive back Asa Jackson also was suspended four games Tuesday for violating the NFL policy on performance-enhancing drugs, depleting an already thin secondary.
Baltimore's once feared-defense ranks 24th overall (375.9 yards per game) and 25th against the run (129.3).
"This is by far one of those years,'' safety Ed Reed said. "I think when coach first got here, second year, we had a lot of injuries. But not like this.''
Denver, meanwhile, is one of two teams to be among the top 10 in both total offense and defense, ranking fourth in each category. Knowshon Moreno ran for 119 yards and a touchdown against Oakland - the second-highest rushing total of his career.
"I think any quarterback would tell you that his best friend is a good running game,'' Manning said. "It's a tough bunch against the run, starting in Baltimore, but we feel it's important, like all season, to be balanced."
Ravens running back Ray Rice, who had a season-high 121 yards last week, rushed for 133 yards and a touchdown in a 31-17 win over Denver in the most recent meeting Oct. 10, 2010.