On paper, this is a total mismatch. The Broncos finished with the best record in the AFC last season at 13-3, and they look even better this year. The Raiders were expected to compete for the No. 1 overall pick but are coming off a win against Jacksonville following a solid showing in Week 1 against the Indianapolis Colts.
Manning is on pace to shatter the single-season touchdown record through two weeks. His performance also has him as the front-runner for his fifth NFL Most Valuable Player award.
Terrelle Pryor has led the Raiders to becoming one of the league's top rushing attacks, but Denver has the No. 1 run defense. He will have a hard time doing anything in this game as his defense will put the team in a big hole.
Below is a list of predictions for the top fantasy stars as well the final score for the game.
Peyton Manning, QB, Denver Broncos
Manning has been incredible at home since signing with Denver. He has thrown for 313 yards per game and has been outstanding in the regular season. The 37-year-old has 29 touchdowns to only three interceptions in nine regular-season home games with the team.
Against Oakland last season, Manning averaged 324 passing yards and threw for a total of four touchdowns and an interception.
The addition of Wes Welker and the emergence of Julius Thomas has made it impossible for teams to contain Manning this year. He has so many weapons to throw to, and he continues to make smart decisions with the football.
Oakland's pass defense ranks third in the league, but that's misleading. The Raiders played the Jaguars last week, so the numbers will look good right now.
Look for the quarterback to have a huge game as he leads his team to a big win before taking his foot off the gas late.
Fantasy projections: 330 passing yards, 4 TD, 0 INT (29 points)
Demaryius Thomas, WR, Denver Broncos
It's tough to figure out whom Manning will utilize the most, but Demaryius Thomas will be a playmaker in this contest. The receiver has turned into a big-play threat every time he touches the ball.
Thomas has averaged 21.3 yards per catch and has two touchdowns through the first two weeks. The 25-year-old had 10 receptions for 186 yards but did not have a touchdown in two games against Oakland last season.
At 6'3" with excellent strength and athleticism, Thomas will have his way with the Raiders secondary. He has turned into one of the best receivers in the league with Manning throwing the ball, and he has the potential to be one of the top stars in this game.
Fantasy projections: 5 receptions, 72 receiving yards, 1 TD (13 points)
Wes Welker, WR, Denver Broncos
Manning's favorite target on the night will be Wes Welker. The veteran has gotten off to a slow start in terms of yards this season with 12 catches for 106 yards, but has three touchdowns in his first two games with Denver and should find more success in prime time.
Monday night will be a breakout performance for Welker, and fantasy owners everywhere will rejoice.
Welker had 67 and 39 yards in the first two games respectively. He was held under 70 receiving yards in back-to-back games only twice last season. Considering he hasn't gone three consecutive games under that mark since 2010, he is due for a big game this week.
Oakland will have its hands full trying to contain all of the different playmakers Denver puts on the field, and Welker will be able to slip open.
Fantasy projections: 8 receptions, 108 yards, 2 TD (22 points)
Denver enters the game as a big favorite for a reason. It has a loaded offense and will be able to do what it wants against Oakland.
Since joining the Broncos, Manning has been incredible at home. He has the team scoring 34.4 points per game at home, and the offense hasn't been held to under 30 points in Denver in exactly one year. Houston held the Broncos to 25 points in Manning's third game with the team, which was also the only game the Broncos lost at home in the regular season.
Through two games this season, the Broncos are averaging 45 points per game this season. Although teams have been able to hang around with Denver in the first half of games, the Broncos have pulled away from teams in the second half as they have scored 66 points in the final 30 minutes through two weeks.
Denver beat up on Oakland last season. In two meetings last year, the Broncos won by an average score of 31.5-9.5, including a 37-6 beating at home.
Pryor won't be able to keep up with Manning. As impressive as the second-year quarterback has been in two starts, the Raiders still rank last in passing yards. He has done well on the ground and enters Monday night's game only 15 yards behind Darren McFadden for the team lead in rushing yards.
Even though the young quarterback may be able to total around 275 total yards, he's going to have a tough time getting his team in the end zone. Pryor has found the end zone only once this year.
Denver is the best team in the AFC, and it will show on Monday night.
Prediction: Denver Broncos 38 - Oakland Raiders 13
*All stats are courtesy of NFL.com