The 49ers will play the NFC South and AFC East, six games within the NFC West, and the last place teams within the NFC.
| Home | Away |
| Dallas Cowboys | Atlanta Falcons |
| New England Patriots | Carolina Panthers |
| New Orleans Saints | Buffalo Bills |
| New York Jets | Miami Dolphins |
| Tampa Bay Buccaneers | Chicago Bears |
| Arizona Cardinals | Arizona Cardinals |
| Seattle Seahawks | Seattle Seahawks |
| St. Louis Rams | St. Louis Rams |
The actual dates and times of each game will be known once the complete NFL schedule is released sometime in April.
Of course, who knows who their head coach will be once that season begins? The 49ers are expected to part ways with head coach Jim Tomsula following the team's season finale against the St. Louis Rams at Levi's Stadium.