2021 NFL Schedule: San Francisco 49ers game-by-game and win-loss record predictions

Last season, the injury bug ruined any playoff chances the San Francisco 49ers may have had. Three of their star players all went down injured -- quarterback Jimmy Garoppolo, tight end George Kittle and defensive end Nick Bosa.

All three return this season and the Niners will be eyeing another long playoff run.

There was some drama this offseason in the bay as the San Francisco 49ers traded up to number three in this year’s NFL Draft. They selected rookie quarterback Trey Lance, which put Garoppolo's future with the team under the spotlight.

Head coach Kyle Shanahan has stated that Garoppolo will be with the team in 2021 but if he gets injured again or struggles on the field he may be cut at any time. The Niners will be hoping he can regain the form that got them to the Super Bowl in 2019.

Let’s take a closer look at the San Francisco 49ers' 2021 NFL schedule and predict how they could perform this season.

Week 1 - Sept. 12: at Detroit Lions

The Niners start the 2021 NFL season on the road in Detroit. The new-look Lions will be a tough test for San Francisco but one they should be able to pass. Jimmy Garoppolo will want to show the San Francisco 49ers and the rest of the NFL that he still has a lot to offer. I see the 49ers winning a close one with a late field goal.

Week 2 - Sept. 19: at Philadelphia Eagles

San Francisco is on the road again in Week 2, this time traveling to Philadelphia. The Eagles had a hectic offseason and are looking to rebuild quickly with new quarterback Jalen Hurts. Nick Bosa will have a big day in Philly and cause havoc for Hurts to help the 49ers start 2-0 this season.

Week 3 - Sept. 26: vs. Green Bay Packers

The San Francisco 49ers host the Green Bay Packers on Sunday Night Football in Week 3. It’s the first home game for San Francisco and I expect Levi Stadium to be jam-packed for this big clash. This will be an offensive affair, with the 49ers squeaking out a hard-fought win at home to continue their unbeaten start to the season.

Week 4 - Oct. 3: vs. Seattle Seahawks

NFC West rivals the Seattle Seahawks arrive at Levi's Stadium in Week 4. Russell Wilson is always hard to beat and this will be another epic divisional game. The San Francisco 49ers offense will do just enough to hold off the Seahawks to go 4-0 in 2021.

Week 5 - Oct. 10: at Arizona Cardinals

The Niners head back on the road to Arizona in Week 5. After beating divisional rivals Seattle, the San Francisco 49ers will struggle away from home. Kyler Murray will step, spin and throw his way to a big home win for the Cardinals. San Francisco will suffer their first defeat of the season.

Week 6 - Oct. 17: BYE

Week 7 - Oct. 24: vs. Indianapolis Colts

The bye week comes at the perfect time for the San Francisco 49ers. They can rest up and recharge before a big game at home against the Colts. Carson Wentz will not have an enjoyable time at bay as Nick Bosa and the Niners’ defense harass him all game. The 49ers return to their winning ways in Week 7.

Week 8 - Oct. 31: at Chicago Bears

It’s never a fun trip to Chicago to face the Bears at Soldier Field. Rookie quarterback Justin Fields has taken over the offense in the windy city and added extra explosiveness to the team.

The Bears’ defense will come up big at home, not allowing Jimmy Garoppolo any time to throw the ball. The San Francisco 49ers fall to 5-2 in Week 8.

Week 9 - Nov. 7: vs. Arizona Cardinals

After losing to the Cardinals in Week 5, the San Francisco 49ers will be determined to avenge the loss. Unlike the previous meeting, Kyler Murray will not run all over the field. San Francisco’s defense will step up big time and lead them to a big divisional victory at home.

Week 10 - Nov. 15: vs. Los Angeles Rams

It’s a battle of California in Week 10 as Sean McVay and the L.A. Rams arrive for a big game in front of a national NFL audience. Matthew Stafford will prove why the Rams traded for him in the offseason with a big performance at San Francisco’s home ground. The Niners lose for just the third time this season.

Week 11 - Nov. 21: at Jacksonville Jaguars

A road trip to Jacksonville to face the young Jags will be seen as a must-win game by the Niners. Nick Bosa will be licking his lips at the prospect of chasing Trevor Lawrence around the field. Garopollo and George Kittle will combine for a big game to lead San Francisco to another road win.

Week 12 - Nov. 28: vs. Minnesota Vikings

Kirk Cousins and the Vikings roar into Levi's Stadium in Week 12. The San Francisco 49ers will be ready for the Minnesota onslaught and hold on for a close home win. Jimmy Garoppolo will again play well, raising hopes of a playoff berth.

Week 13 - Dec. 5: at Seattle Seahawks

A December road trip to Seattle is a daunting task for any team. The Seahawks will want to beat the San Francisco 49ers at home to boost their playoff hopes. Russell Wilson, D.K. Metcalf and Tyler Lockett will all have big games as they dominate the Niners in front of their home fans.

Week 14 - Dec. 12: at Cincinnati Bengals

After a big road loss to NFC West rivals the Seahawks, the San Francisco 49ers will get back on the winning track in Cincinnati. Joe Burrow and his young squad won’t have enough offensive power to beat San Francisco. The 49ers move to 9-4.

Week 15 - Dec. 19: vs. Atlanta Falcons

The San Francisco 49ers' successful season will continue with a home game against the Atlanta Falcons. George Kittle will have yet another big game going for over 100 yards against the Falcons defense. San Francisco will get their 10th win in front of their fans.

Week 16 - Dec. 23: at Tennessee Titans

San Francisco’s winning streak will come to an end on Thursday Night Football in Tennessee. The Titans, led by Ryan Tannehill and Derrick Henry, will show a national audience why they are a force in 2021 and provide a reality check for the San Francisco defense.

Week 17 - Jan. 2: vs. Houston Texans

The Niners face the Houston Texans in their final home game of the regular season. San Francisco should prove to be far too good for a Texans team that is undergoing a rebuild. A dominant win at home is the perfect way to sign off in front of their fans.

Week 18 - Jan. 9: at Los Angeles Rams

It’s a tough end to the regular season for San Francisco 49ers with a road trip to Los Angeles to take on NFC West rivals the Rams. The San Francisco 49ers will once again lose to the Rams and Matthew Stafford. It's not the ideal way to head into the playoffs, but they may get their chance for revenge in the postseason.