Week 1: at Tampa Bay Buccaneers

Steve Mariucci's debut game as 49ers head coach did not go well as Steve Young was sacked by Warren Sapp on San Francisco's first drive and was benched due to injury for Jeff Brohm until the fourth quarter. Brohm made no difference in the 13–6 Bucs win. Jerry Rice’s season all but ended in injury after four catches for 38 yards.

Week 2: at St. Louis Rams

Jim Druckenmiller started for Young as the Niners entered the TWA Dome. The Rams scored first on a field goal while San Francisco's first drive saw a missed attempt; Druckenmiller completed only ten passes (on 28 throws) and three of them were on this drive but later in the second he completed a 25-yard touchdown (it would be the only touchdown of his NFL career). The Rams led 12–7 on four Jeff Wilkins field goals until after a Lawrence Phillips fumble with 12 minutes remaining, when Garrison Hearst burst in a 35-yard Niners score on the resulting San Francisco possession. The Rams failed on fourth down in the final five minutes to seal the 15–12 Niners win.

Week 3: vs. New Orleans Saints

The Niners' first home game of the year was another win over the Saints, who were led this time by ex-Bears coach Mike Ditka. Despite being sacked five times Steve Young completed eighteen passes for 220 yards and three touchdowns. Saints quarterbacks threw a combined six interceptions in the game.

Week 4: vs. Atlanta Falcons

Young again blew past 30 points scored as the Niners routed the Falcons 34–7. Young completed 17 of 24 passes for 336 yards and two touchdowns, one a 56-yarder to Terrell Owens.

Week 5: vs. Carolina Panthers

After just one win in four career games against the Panthers in Carolina's first two seasons, the Niners upended the slumping Panthers 34–21. The Niners jumped to a 27–7 lead as they intercepted Kerry Collins three times.

Week 7: vs. St. Louis Rams

The Niners crushed the Rams at 3Com Park 30–10 as they held Tony Banks to just nine completions while sacking him four times.

Week 8: at Atlanta Falcons

A week after getting their first win of the season (against New Orleans) the Falcons hosted the Niners and their first drive ended in a 27-yard touchdown throw by Jamal Anderson to Bert Emanuel. The Niners scored three straight touchdowns and kept answering ensuing Falcons touchdowns with more of their own. With the score 35–28 San Francisco, the Falcons attempted an onside kick but the Niners recovered and won the game.

Week 9:at New Orleans Saints

The Niners traveled 470 miles southwest to the Superdome and flustered the 2–6 Saints yet again. Three Saints quarterbacks could only muster 109 yards with a pick and a fumble as the Niners rolled 23–0.

Week 10: vs. Dallas Cowboys

The playoff-level intensity of the 1992–96 period was gone as the faltering Cowboys limped into 3Com Park at 4–4 and led in the third quarter 10–7, but the surging Niners scored ten more points and then intercepted Troy Aikman in the game's final minute on a pass intended for Stepfret Williams. The 17–10 Niners win would in essence be a last hurrah for the rivalry that had dominated the league earlier in the decade. It was also the 49ers' last win over the Cowboys at home until 2022.

Week 11: at Philadelphia Eagles

The Niners traveled to Veterans Stadium and won 24–12, snaring three Eagles turnovers and scoring on a Merton Hanks fumble return and a Chuck Levy punt return.

Week 12: vs. Carolina Panthers

The Niners picked off Kerry Collins three more times and held the Panthers under 260 total yards as they reached ten straight wins 23–19.

Week 13: vs. San Diego Chargers

The collapse of San Diego's season after a 4–4 start continued as only a Paul Bradford fumble-return score marred San Francisco's 17–10 win.

Week 14: at Kansas City Chiefs

Three years after their loss to Joe Montana at Arrowhead Stadium, the Niners were crushed 44–9 as Rich Gannon threw three touchdowns and Steve Young threw three interceptions, and Jeff Brohm threw a pick-six.

Week 15: vs. Minnesota Vikings

Steve Young rebounded with two touchdowns in a 28–17 win over the Vikings. In a harbinger of the Vikings' subsequent season, Randall Cunningham played the whole game and had two touchdowns.

Week 16: vs. Denver Broncos

The Niners reached thirteen wins by crushing the Super Bowl-bound Denver Broncos 34–17. The Broncos led 17–14 in the third quarter but after a Niners field goal John Elway was picked off by Merton Hanks and Hanks scored. Another Niners field goal and a fumble-return score by Kevin Greene salted away the San Francisco win. Jerry Rice returned for this one game and had three catches and a touchdown.

Week 17: at Seattle Seahawks

Having secured the top playoff seed, the Niners played all three of their quarterbacks at the Kingdome, and the frustrated Seahawks ended their 8–8 season on a high note as Warren Moon erupted for four touchdowns in only his second career win (38–9) in six games against San Francisco (the other win was a 10–7 win with the Oilers in 1993).

NFC Divisional Game vs. (6) Minnesota Vikings

NFC Championship Game vs. (2) Green Bay Packers

The 49ers and Packers met in the playoffs for the 3rd year in a row, and for the 3rd year in a row, the Packers defeated the 49ers. The 49ers were battling multiple injuries in the game, including missing star wide receiver Jerry Rice. The lack of depth on offense showed throughout the game, as the offense generated just 3 points. The only touchdown of the game for the 49ers was Chuck Levy's 95-yard kick return for a touchdown. But by then, the Packers had a commanding 23–10 lead in the 4th quarter. With the loss, the 49ers finished the year at 14–4.