San Francisco 49ers vs. Buffalo Bills Betting Odds, Analysis, NFL Pick

The San Francisco 49ers will be looking to end a four-game straight-up and against-the-spread losing streak when they visit the Buffalo Bills on Sunday.

The 49ers have surrendered 35 points per game since opening with a 28-0 win over the Los Angeles Rams and are 1-9 SU and 2-8 ATS in their past 10 road contests. The Bills have claimed decisive victories in three straight games, including two outright wins as betting underdogs, and they are 14-2 SU and 10-6 ATS in their past 16 games when favored by nine or more points.

Point spread: The Bills opened as seven-point favorites; the total was 45.5 early in the week, according to sportsbooks monitored by Odds Shark (Line updates and matchup report).

NFL pick, via Odds Shark computer: 25.0-17.0 Bills (NFL picks on every game)

Why the 49ers can cover the spread

Colin Kaepernick takes over under center for the Niners for the ineffective Blaine Gabbert, and he will be counted on to recapture the magic of his 2014 season, when he threw 19 touchdown passes while leading the team to eight wins.

Running back Carlos Hyde has scored in each of his last three outings and will challenge a Bills rush defense that has surrendered more than 100 yards in three of the past four games.

The Niners' pass defense has held opponents to an average of just 175 yards in the past two outings and will need to stand tall against the Bills' underachieving aerial game, which is ranked 31st in the NFL after being held to 112 or fewer yards on three occasions this season.

Why the Bills can cover the spread

After opening the season with a pair of ugly SU and ATS loss, the Bills have bought into head coach Rex Ryan's game plan.

Buffalo has held opponents to just over 12 points per game during its win streak while forcing 11 turnovers. That is bad news for the 49ers, who have coughed up the ball eight times during their current slide, including a fumble and two interceptions in last week's 33-21 loss to the Arizona Cardinals.

The Bills have also been beasts in their own red zone, stopping opponents on 10 of 16 drives inside the 20-yard line and forcing four turnovers inside their own 30 in their last home game, a 33-18 win over Arizona three weeks ago.

Smart pick

With their dominating play in recent weeks, the Bills are shaking their reputation as pretenders and have quickly emerged as a feared opponent in their own building, where they are a strong 5-1 SU and ATS in their past six outings.

The 49ers have taken three of four SU from Buffalo but are in a downward spiral that is unlikely to end against the ferocious Bills. Look for the Bills to extend San Francisco's misery with a solid SU and ATS win, even with the spread on the move in their direction.

Betting trends

The 49ers are 3-1 SU and ATS in their last four games against the Bills.

The total has gone over in six of the Bills' last seven games as the favorite.

The Bills are 1-9 SU and 2-7-1 ATS in their last 10 games after consecutive wins.

All NFL betting lines and point spreads data courtesy of Bleacher Report’s official odds partner, Odds Shark. All quotes gathered firsthand unless otherwise noted. Check out Twitter for injury and line movement updates and Odds Shark YouTube for picks and analysis, or download the free odds tracker app.