Thursday Night Football: San Francisco 49ers-Los Angeles Rams betting preview (odds, lines, best bets)

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- Kyle Shanahan and Sean McVay are familiar with each other: Dating back to when both were hired as head coaches in 2017, seven of their 17 games have been decided by three or fewer points, including their most recent matchup in LA during Week 3 of last season — a game the Rams won outright as six-point dogs.
- Kyren Williams could have success on outside zone runs: Williams has excelled on those looks this season, as he sports an NFL-best 86.3 PFF rushing grade on outside zone runs — totaling 5.7 yards per carry.
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Estimated Reading Time: 4 minutes

San Francisco 49ers vs Los Angeles Rams (-6.5) [Total: 46.5]
Game Overview
Sean McVay and Kyle Shanahan have a long history as both colleagues and adversaries. They’re no stranger to the inner workings of each other’s schemes, and as such, have battled it out in numerous hotly contested matchups. Dating back to when both were hired as head coaches in 2017, seven of their 17 games have been decided by three or fewer points, including their most recent matchup in LA during Week 3 of last season — a game the Rams won outright as six-point dogs.
Shanahan has, by and large, had McVay’s number when facing off in LA, with the 49ers having won six of nine matchups there and holding a 6-3 record against the spread. However, Mcvay’s Rams have pushed back in recent years, producing three consecutive outright wins as the underdog and two straight covers in LA.
Compared to those previous games, market conditions for this matchup have changed considerably, with the Rams heavily favored. The Rams haven’t been favorites against the 49ers since Week 8 of the 2022 season, and hold just a 2-8 ATS record as the favorite. That trend looks less likely to be the case this time around, with LA holding a strong 3-1 ATS to start the year — with all three covers coming as the favorite.
Conversely, the 49ers dropped the cover in each of their last two games, due in large part to a laundry list of injuries that continue to hamper their potential, as they did last season. As it currently stands, this team may be without six of its 10 highest-paid players (in cap hit) — including Brock Purdy, after reaggravating a toe injury in his Week 4 return. That comes in addition to the possible absence of both Ricky Pearsall and Jauan Jennings, who have been two of the offense’s top playmakers.
That news has swung this line drastically toward the Rams after opening at around 3.5 points on Sunday.
RB Kyren Williams, Los Angeles Rams: Over 66.5 rushing yards (-114)

The Rams have been running the ball well to start the year, behind some strong performances from Kyren Williams and the second-highest graded run-blocking offensive line (77.3) in the NFL. Williams holds the fifth-highest PFF rushing grade (79.6) through September, with impressive outings in back-to-back games, putting up over 75 rushing yards in each. His prior two games were still solid performances that landed just under this line at 66 yards, so he’s trending in the right direction.

The 49ers have had difficulty stopping the run, surrendering 124 yards to Travis Etienne Jr. this past week. They particularly have issues against outside zone, having permitted the highest yards-per-carry average (6.5) and the third-highest successful play rate (43.5%), resulting in the lowest PFF run-defense grade (38.9) against it.
That is a spot the Rams can attack this 49ers defense, having run the eighth-highest rate of outside zone (36%) this season. Williams has excelled on those looks this season, as he sports an NFL-best 86.3 PFF rushing grade on outside zone runs — totaling 5.7 yards per carry.
