The Packers had the best record in the league last season (15-1), while the 49ers emerged out of mediocrity under first-year head coach Jim Harbaugh to shock everyone, posting a 13-3 record and making it to the NFC Championship Game.
Many are picking the Packers to win the Super Bowl this season, but don't think the 49ers, or the reigning champion New York Giants, are going to let them get out of the NFC unscathed.
Here's a preview of what should be a fantastic opening game at Lambeau Field.
Where: Lambeau Field, Green Bay, WI
When: Sunday, Sept. 9 at 4:25 p.m. ET
Betting Line: Packers -5, Over/Under 47, via Bovada
What's At Stake?
This game may not only be a preview of the NFC Championship Game this season, it also could end up determining home-field advantage in the playoffs.
The Packers captured home-field advantage with a 15-1 record last season, with the upstart 49ers going 13-3 under first-year head coach Jim Harbaugh.
Nonetheless, it was the 49ers who went deeper in the postseason, making it to the NFC Championship Game before getting knocked out by Eli Manning and the eventual-champion New York Giants. That was after the Giants disposed of the Packers in the divisional playoffs.
Coaches and players will tell you every game is important, but there is no denying the potential significance of this matchup.
Injury Report (via USA Today)
WR Ted Ginn Jr - Ankle - Questionable
RB Brandon Jacobs - Knee - Questionable
LB Darius Fleming - Knee - OUT indefinitely
RB Jewel Hampton - Knee - OUT indefinitely
LB Parys Haralson - Undisclosed - IR
NT B.J. Raji - Ankle - Questionable
TE Andrew Quarless - Knee - OUT indefinitely
LB Frank Zombo - Hamstring - OUT indefinitely
LB Desmond Bishop - Hamstring - IR
DL Johnny Jones - Knee - IR
OT Ray Dominguez - Ankle - IR
WR Shaky Smithson - Ankle - IR
TE Demarco Cosby - Hamstring - IR
RB Duane Bennett - Knee - IR
What They're Saying
Haralson, who will be replaced by 13-year veteran Clark Haggans as he serves time on injured reserve, was part of a 49ers defense that allowed just 3.5 yards per carry last season, tops in the NFL. His loss figures to be felt.
The extent of the drop-off depends on Haggans, who has played with the Arizona Cardinals and Pittsburgh Steelers. The 35-year-old registered 46 tackles (two tackles for loss), three sacks and a forced fumble last season with the Cardinals.
As for the Packers, they are counting on second-year pro D.J. Smith to anchor the middle of the field with starting inside linebacker Desmond Bishop on injured reserve.
Packers defensive coordinator Dom Capers said, via the Journal Sentinel:
I like D.J. He's a consistent guy. The game's not too big for him. He's done a nice job when he's had the opportunity.
Bishop was one of the Packers' best playmakers on defense last season. He racked up 115 tackles (five tackles for loss), five sacks and two forced fumbles.
Smith posted 43 tackles (one tackle for loss) and an interception.
Smith will be a big part of the Packers trying to stop the 49ers' running game, which comes complete with Frank Gore and promising youngster Kendall Hunter.
49ers Player to Watch: Patrick Willis, LB
There are so many candidates for this spot (including quarterback Alex Smith, whose play this season is key for the 49ers), but how can you leave Patrick Willis out?
Willis has emerged as the best linebacker in football. He racked up 128 tackles (five tackles for loss), six sacks and two forced fumbles in 2010. He followed that up with 97 tackles (five tackles for loss), two sacks, four forced fumbles and an interception last season, despite playing alongside NaVorro Bowman and Aldon Smith.
The 49ers' linebackers unit is scary good and Willis is the force that drives it.
Packers Player to Watch: Aaron Rodgers, QB
Aaron Rodgers has established himself as arguably the best quarterback in football.
He led the Packers to a 15-1 record last season, throwing for over 4,600 yards and 45 touchdowns to six interceptions, while completing 68 percent of his passes for 9.25 yards per attempt (the best mark in football by a long shot).
The last time Rodgers faced the 49ers, he went 21-of-30 for 298 yards and three touchdowns. Of course, this is an entirely different 49ers defense than the one that took the field in 2010.
Key Matchup: 49ers Passing Game vs. Packers Defense
Who are we kidding? Rodgers will likely play well. Gore will likely rack up chunks of yards. The real difference may come in Alex Smith's ability to find his receivers against the Packers' defense.
Green Bay wasn't the elite defensive unit last season that it was when it won the Super Bowl in 2011. The Packers allowed 1.23 points per drive last season (23rd in the NFL) and gave up 35.64 yards per drive (29th), per FootballOutsiders.com.
The Packers also allowed opposing quarterbacks to complete 61.2 percent of their passes (19th) and gave up 7.8 yards per attempt (27th).
Smith is coming off a career year in which he completed 61 percent of his passes for over 3,100 yards while throwing 17 touchdowns to just five interceptions. He's a completely different quarterback than he was in the past.
Who will win?
Prediction: Packers 24, 49ers 20
This should be a fantastic game and I expect it to go down to the wire. In the end, I think Rodgers will do just enough against the vaunted 49ers defense to eke out a win. Playing at Lambeau Field will certainly help. Smith is a good quarterback now, but playing at Lambeau Field is a completely different environment and he's still developing a rapport with new receivers Moss and Manningham.