San Francisco 49ers running back Christian McCaffrey (23) runs against Seattle Seahawks cornerback Coby Bryant (8) during the second quarter at Levi's Stadium in San Francisco, California.

The San Francisco 49ers and the Seattle Seahawks open their seasons Sunday. Kickoff from Lumen Field is scheduled for 4:05 p.m. ET (FOX). Let's analyze BetMGM Sportsbook's NFL odds around the 49ers vs. Seahawks odds and make our expert NFL picks and predictions for the best bets.

The 49ers reshaped their roster this offseason, trading WR Deebo Samuel to the Washington Commanders and reuniting with former New York Jets coach Robert Saleh, who returns as defensive coordinator. Free agency departures included LB Dre Greenlaw, S Talanoa Hufanga, CB Charvarius Ward and G Aaron Banks, while San Francisco added RB Brian Robinson Jr. from the Commanders. The 49ers stumbled to a 6-11 finish in 2024, last in the NFC West, as injuries to stars such as RB Christian McCaffrey, WR Brandon Aiyuk and OT Trent Williams derailed their season.

The Seahawks dealt QB Geno Smith to the Las Vegas Raiders and signed QB Sam Darnold, WR Cooper Kupp and DE DeMarcus Lawrence. Seattle finished 10-7 last season, placing second in the division after losing a strength-of-victory tiebreaker to the LA Rams, and missed the playoffs for the second straight year.

The NFC West rivals split their 2 games in 2024, each winning on the road. The 49ers won 36-24 in Week 6 on Thursday Night Football and the Seahawks won 20-17 in Week 10.

Play to win $5K: USA TODAY NFL Survivor contest

49ers at Seahawks odds

Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated at 12:21 a.m. ET.

  • Moneyline (ML): 49ers -118 (bet $118 to win $100) | Seahawks -102 (bet $102 to win $100)
  • Against the spread (ATS): 49ers -1 (-110) | Seahawks +1 (-110)
  • Over/Under (O/U): 43 (O: -110 | U: -110)

WIN YOUR FANTASY FOOTBALL LEAGUE! The Huddle has been turning players like you into winners for over 25 years. This season, it's your turn. Custom fantasy football rankings, sleepers and tools are just a click away. Subscribe now!

49ers at Seahawks key injuries

49ers

  • WR Brandon Aiyuk (knee) out
  • RB Christian McCaffrey (calf) questionable; expected to play barring setbacks

Seahawks

  • None

49ers at Seahawks picks and predictions

Prediction

49ers 21, Seahawks 20

Moneyline

SAN FRANCISCO (-118) deserves to be favored, with a healthier roster than a year ago. While the 49ers may not be dramatically stronger than Seattle on paper, the Seahawks could need time to adjust after swapping Smith for Darnold this offseason. If this matchup came in Week 6 or later, I’d lean toward Seattle as an underdog, but San Francisco’s continuity makes the difference this early in the year.

Seattle’s home-field edge is also a thing of the past. Former players often call it one of the league’s toughest venues, yet the numbers don’t back that up -- the Seahawks are just 13-20-1 ATS at home since 2021, proof the impact of the 12s has been overstated for years.

BET 49ERS (-118).

Against the spread

I prefer the moneyline, as it's more likely to win, but I'm not against laying the point and risking a push.

LEAN 49ERS -1 (-110).

Play our free daily Pick’em Challenge and win! Play now!

Over/Under

McCaffrey's calf injury is expected to have a small negative impact on the 49ers offense -- and Aiyuk on the reserve/PUP list doesn't help either.

On the other side, Darnold does have familiarity with offensive coordinator Klint Kubiak from their time together in San Francisco, but it’s highly unlikely he’ll match the production he showed last season under Minnesota Vikings coach Kevin O’Connell.

BET UNDER 43 (-110).

For more sports betting picks and tips, check out SportsbookWire.com and BetFTW.

Follow @corey_a_scott on Twitter/X. Follow SportsbookWire on Twitter/X and like us on Facebook.

Access more NFL coverage:

TheHuddle Fantasy Football | BearsWire | BengalsWire | BillsWire | BroncosWire | BrownsWire | BucsWire | CardsWire | ChargersWire | ChiefsWire | ColtsWire | CommandersWire | CowboysWire | DolphinsWire | EaglesWire | FalconsWire | GiantsWire | JaguarsWire | JetsWire | LionsWire | NinersWire | PackersWire | PanthersWire | PatriotsWire | RaidersWire | RamsWire | RavensWire | SaintsWire | SeahawksWire | SteelersWire | TexansWire | TitansWire | VikingsWire | DraftWire | TouchdownWire | ListWire

This article originally appeared on Sportsbook Wire: San Francisco 49ers at Seattle Seahawks odds, picks and predictions

Reporting by Corey Scott, Sportsbook Wire / Sportsbook Wire

USA TODAY Network via Reuters Connect