San Francisco 49ers vs. Arizona Cardinals Betting Odds, Analysis, NFL Pick

The worm may be turning in the rivalry between the 49ers and Cardinals; San Francisco has won 10 of the last 12 meetings between the teams, but Arizona is 4-3 against the spread over the last seven, including an ATS sweep of the series last season. First-place Arizona hosts the Niners Sunday afternoon.

Point spread: The Cardinals opened as six-point favorites; the total was 44.5 early in the week, according to sportsbooks monitored by Odds Shark. (Line updates and matchup report)

NFL pick, via Odds Shark computer: 29.1-20.3 Cardinals

Why the 49ers can cover the spread

San Francisco is 1-1 both SU and ATS so far this season after falling at Pittsburgh last week 43-18, whiffing on the cover as a six-point underdog. The 49ers only trailed 8-3 midway through the second quarter, but gave up three touchdowns over a seven-minute span to fall out of contention.

San Francisco actually outrushed the Steelers on the day 111-84, and quarterback Colin Kaepernick threw for 335 yards and two scores, but the Niners defense just couldn't stop Ben Roethlisberger—although that Pittsburgh offense is one of the best in the business at the moment.

San Francisco opened this season with a 20-3 victory over Minnesota, outrushing the Vikings 230-71, winning outright as a two-point home dog.

The 49ers are not the team they were even just one year ago, but if they can get the running game going with Carlos Hyde, avoid the turnovers and play defense like they did against Minnesota, they'll be right in this contest.

Why the Cardinals can cover the spread

Arizona is off to a 2-0 start both SU and ATS after bombing the Bears in Chicago last week 48-23. The Cardinals started fast, as David Johnson returned the opening kickoff 108 yards for a touchdown, then, after leading 28-20 at the half, won the second half 20-3 on their way to covering as two-point road favorites.

Arizona got 72 yards on the ground from newcomer Chris Johnson, while quarterback Carson Palmer threw four touchdown passes against one pick. The Cardinals are now 18-6 SU and 18-5-1 ATS when Palmer starts behind center.

Arizona opened this season with a 31-19 victory over New Orleans, also covering as a two-point favorite.

The Cardinals are contenders in the NFC and would love nothing more than to take the upper hand in the series with San Francisco. They split two games with the Niners last season, the loss coming by a field goal and Palmer missing both games. With him, they're tough.

Smart pick

Arizona is on the rise, while San Francisco is on the fade. But the NFL is a fickle betting proposition; teams that look great one week often suffer letdowns the next, and vice versa. And the Cardinals, while a very good team, are not immune to those ups and downs. The smart money in this situation probably resides with the 49ers, plus the points.

Betting trends

The 49ers are 8-2 ATS in their last 10 games on the road against the Cardinals.

The total has gone under in seven of the 49ers’ last nine games.

The Cardinals are 7-1 SU in their last eight games as September favorites.

All point spread and lines data courtesy of Odds Shark, all quotes gathered firsthand unless otherwise noted. Check out Twitter for injury and line movement updates and get the free odds tracker app.