It's the latest game in a postseason rivalry that rose to center stage in the 1990s, with both teams led by legendary quarterbacks in Steve Young and Brett Favre. The rivalry has been renewed multiple times in the 21st century.
Saturday will be the ninth playoff meeting between these teams, tied with the Dallas Cowboys and Los Angeles Rams as the most common playoff matchup in NFL history. The squads have split the previous eight meetings, with the 49ers riding a three-game postseason win streak that dates back to 2012.
Here are some defining moments between the familiar foes, selected by NFL Nation reporters Rob Demovsky and Nick Wagoner.
1995 NFC divisional round
The team's first postseason meeting was also the first time Green Bay head coach Mike Holmgren coached against San Francisco, where he was the offensive coordinator and quarterbacks coach from 1986 to 1991 and won two Super Bowls.
This game was all Green Bay.
The Packers' defense tallied four turnovers. The party began when LB Wayne Simmons forced a fumble on San Francisco's first offensive snap that CB Craig Newsome returned for a touchdown. The Packers used their hot start to build a 21-0 lead in the first half. San Francisco QB Steve Young attempted a playoff-record 65 passes, but it still wasn't enough to come out on top as the defending Super Bowl champions lost 27-17.
1996 NFC divisional round
Nicknamed the Mud Bowl because of sloppy conditions at Lambeau Field, this was the Packers' first postseason win on the way to winning Super Bowl XXXI. Similar to their last divisional-round meeting, Favre & Co. jumped out to a three-touchdown lead in the first half. But this time around, two Green Bay turnovers aided San Francisco's efforts at a comeback and the lead shrunk to 21-14.
Once again, the Packers' defense helped the scoring efforts by recording five takeaways against a Niners offense that was without Steve Young for most of the game because of cracked ribs.
Green Bay scored the final 14 points and won 35-14.
1997 NFC Championship Game
Green Bay was the reigning Super Bowl champion but had to travel to Candlestick Park in the postseason.
The visiting team held a 13-3 lead at the half, but a scoreless third quarter kept the game within reach for San Francisco.
The Packers added 10 points in the fourth quarter before their opponent found the end zone for the first time via RB Chuck Levy's 95-yard kickoff return for a touchdown.
It was too little, too late, as Green Bay cruised to its third consecutive playoff win over San Francisco 23-10.
Packers safety LeRoy Butler, creator of the Lambeau Leap, grew fond of meeting a familiar face in the postseason.
"I probably liked playing San Francisco more than anybody else," Butler told Forbes in 2020. Beating them was so satisfying, because I knew all those guys would be in the Hall of Fame. The quarterback, the receivers, the linebackers, the coach, the owner."
1998 NFC wild-card round
Unlike their previous postseason matchups, the fourth meeting was a back-and-forth battle. It all came down to the final drive.
Jerry Rice's first and only reception of the game came with less than 40 seconds remaining. Despite clearly losing possession of the ball, the officials missed the call and instant replay was not in use at the time, so the drive continued.
Young found Terrell Owens for a 25-yard game-winning toss that was nicknamed "The Catch II" as an ode to Joe Montana and Dallas Clark's connection known as "The Catch" in the 1981 NFC Championship Game against the Dallas Cowboys.
San Francisco ended its three-year postseason skid against Green Bay with a 30-27 victory, and it was a moment that helped make Owens a superstar.
2012 NFC divisional round
This game was the playoff debut of Colin Kaepernick.
In just his eighth NFL start, Kaepernick rushed for a quarterback-record 181 yards and two touchdowns and threw two more TDs to pair with his 263 yards through the air.
San Francisco came out on top 45-31.
2013 NFC wild-card round
The 49ers and Packers faced a frigid kickoff temperature of 5 degrees at Lambeau Field. It turned into a duel between Aaron Rodgers and Kaepernick as well as the teams' kickers.
Rodgers led the offense downfield for a tying field goal by Mason Crosby in the final quarter, but it left over five minutes on the clock for Kaepernick's squad. San Francisco's ensuing drive included four consecutive carries by Frank Gore that forced Green Bay to exhaust all three timeouts.
Phil Dawson's 33-yard, go-ahead field goal was the difference-maker that lifted the Niners over the Packers 23-20.
2019 NFC Championship Game
This matchup was decided early as the 49ers led 27-0 at halftime.
Raheem Mostert ran all over Green Bay, gaining 220 rushing yards with four scores. As a result of the dominant run game, Jimmy Garoppolo threw only eight passes, tied for the second-fewest passes thrown in a playoff game. He even went 24 minutes of game time between his sixth and seventh passes.
San Francisco's 37-20 win sent the 49ers to the Super Bowl, where they eventually lost to the Kansas City Chiefs.