The San Francisco 49ers head down the 101 freeway to visit Southern California as they battle the Los Angeles Rams at Sofi Stadium. We're in Inglewood sharing our NFL odds series, making a 49ers-Rams prediction and pick while showing you how to watch.

The 49ers demolished the Pittsburgh Steelers 30-7 in Week 1. Amazingly, they dominated from start to finish. Brock Purdy went 19 for 29 with 220 yards and two touchdowns. Meanwhile, Christian McCaffrey rushed 22 times for 152 yards and a touchdown while catching three passes for 17 yards. Brandon Aiyuk led all receivers with eight catches with 129 yards and two touchdowns. Additionally, Deebo Samuel had five catches for 55 yards while rushing twice for eight yards. George Kittle had three catches for 19 yards. Ultimately, they went 6 for 13 on third-down conversions while going 1 for 1 on fourth down.

The Niners had 188 rushing yards. However, they allowed three sacks. The 49ers thrived on defense, notching five sacks, with Drake Jackson getting three of them. But the Niners also had 11 penalties.

The Rams defeated the Seahawks 30-13. Initially, they trailed 13-7 at halftime. But they rammed through the Hawks in the second half  for a 23-0 win. Significantly, Matthew Stafford went 24 for 38 for 334 yards. Kyren Williams rushed 15 times for 52 yards and two touchdowns, while Cam Akers ran 22 times for 29 yards and a touchdown. Tutu Atwell caught six passes for 119 yards. Additionally, Puka Nacua caught 10 passes and 119 yards in his NFL debut.

The Rams went 11 for 17 on third-down conversions. Also, they converted their lone fourth down. The Rams also did not allow a sack. However, they also had seven penalties. Aaron Donald had half a sack.

The 49ers lead the all-time series 77-68-3. Additionally, San Francisco has won eight regular-season games in a row.

Here are the 49ers-Rams NFL odds, courtesy of FanDuel. 

NFL Odds: 49ers-Rams Odds

San Francisco 49ers: -7 (-110)

Los Angeles Rams: +7 (-110)

Over: 44.5 (-115)

Under: 44.5 (-105)

How to Watch 49ers vs. Rams Week 2

TV: FOX Sports

Stream: fuboTV, NFL+

Time: 4:06 PM ET/1:06 PM PT

*Watch NFL games LIVE with fuboTV (click for a free trial)*

Why The 49ers Could Cover The Spread

The 49ers must continue to run the ball well. Significantly, every win over the Rams has included a great rushing effort. The one loss came in the 2022 NFC Championship Game,  where they could not run the ball. Therefore, the 49ers need to establish the running game.

They did an exceptional job of doing that last season when they gashed the Rams for 111 yards in a win in Los Angeles. Also, they went 5 for 9 on third-down conversions. They allowed three sacks. Also, they only committed three penalties.

But the real star of the show in that game was McCaffrey. Amazingly, he did everything a player could do. McCaffrey went 1 for 1 with a 34-yard touchdown pass. Additionally, he rushed 18 times for 94 yards and a touchdown while also catching eight passes for 55 yards and a touchdown. McCaffrey became the first player since 2005 to accomplish that exceptional feat. Therefore, look for the Niners to involve him heavily again. Kittle will look to do more, as he caught three passes for 39 yards and a score in the win over the Rams last season.

The 49ers will cover the spread if they can run the ball efficiently and avoid Donald. Then, they must stop the running game and force Stafford to throw.

Why The Rams Could Cover The Spread

The Rams must stop the running game. Moreover, they must protect the football and move the chains. They only had 56 rushing yards in a 31-14 loss last season. However, they also went 8 for 13 on third-down conversions while punting five times. But they allowed two sacks and committed four penalties. Stafford went 22 for 33 with 187 yards and a touchdown in that game.

But the Rams won't have the services of Cooper Kupp in this game. Unfortunately, he is out with a hamstring injury. The Rams hope Nacua can make some noise against the Niners. Likewise, they must find ways to keep the hot San Francisco offense off the field. But the most important thing the Rams must do is protect Stafford. Ultimately, it won't be easy with Nick Bosa, Javon Hargrave, and Arik Armstead charging toward them.

The Rams will cover the spread if they can win time of possession. Then, they must stop McCaffrey.

Final 49ers-Rams Prediction & Pick

The Niners and Rams both won their Week 1 openers. However, the 49ers are the superior team. The Rams will keep it close for three quarters. Then, the 49ers will eventually pull away and win this game by at least 10 points. The 49ers cover the spread against their divisional rivals.

Final 49ers-Rams Prediction & Pick: San Francisco 49ers: -7 (-110)