San Francisco 49ers vs. Pittsburgh Steelers Prediction, Odds, Picks

The San Francisco 49ers (0-0) are favored by 2.5 points when they visit the Pittsburgh Steelers (0-0) on September 10, starting at 1:00 PM ET, airing on FOX and the FOX Sports App. 

The 49ers are led by Brock Purdy who hopes to become the latest SF QB to lead his team to the Super Bowl. While, Kenny Pickett looks to fill the formidable footprints of the great quarterbacks in the Steelers' past. 

Here's everything you need to know about the NFL odds for the matchup between the 49ers and Steelers — the point spread, moneyline, total Over/Under and a pick from our betting expert Jason McIntyre. 

49ers vs. Steelers Odds & Betting Lines

49ers vs. Steelers Prediction & Pick

• Pick ATS: San Francisco (-2.5) 
• Pick OU: Under (41.5) 
• Prediction: San Francisco 23 - Steelers 18

Pick via FOX Sports Betting Expert Jason McIntyre:

I've been talking about this game for months on The Herd, and the Steelers are the side for me. That’s regardless of whether TE George Kittle (hamstring) plays or not. 

Expect Nick Bosa to be on a limited snap count, which will hurt a 49ers' defense that has some question marks in the secondary with Charvarius Ward and Talanoa Hufanga missing practice Thursday. 

The 49ers will lose this game in the trenches, where the right side of their line struggles to contain TJ Watt. This season, the Steelers' offense will be more dynamic than the 3-yards and a cloud of dust we’ve seen in recent years from Matt Canada. 

PICK: Steelers (+2.5) to lose by fewer than 2.5 points (or win outright)
PICK: Steelers (-116) moneyline to win outright

How to Watch San Francisco vs. Pittsburgh

• Game Date: Sunday, September 10, 2023
• Time: 1:00 PM ET
• Venue: Acrisure Stadium
• Location: Pittsburgh, Pennsylvania
• TV: Watch on FOX

49ers vs. Steelers Recent Matchups

• San Francisco holds a 3-2 record against Pittsburgh in their last five matchups.
• Over their last five head-to-head matchups, Pittsburgh has scored 117 points, while San Francisco has accumulated 108.

San Francisco Betting Info

• San Francisco won 11 games against the spread last season, failing to cover six times.
• The 49ers' ATS record as 2.5-point favorites or greater was 11-4 last year.
• Last season, nine San Francisco games went over the point total.
• The 49ers finished 13-3 in games they were listed as the moneyline favorite last season (winning 81.2% of those games).
• When it played as a moneyline favorite with odds of -130 or shorter, San Francisco had a 13-2 record (winning 86.7% of its games).
• The implied moneyline probability for this matchup gives the 49ers a 56.5% chance to win.

49ers Stats (2022)

San Francisco's Key Players

Offense

• Last season over 17 games, Christian McCaffrey racked up 1,139 rushing yards (eighth in the NFL) and scored eight rushing touchdowns. He averaged 67.0 yards per game and 4.7 per attempt (18th in the NFL).
• McCaffrey also was a part of the receiving game with 741 yards (43.6 per game) on 85 receptions (5.0 per game), while being targeted 108 times. He had five receiving touchdowns.
• Brandon Aiyuk had 1,015 receiving yards and eight touchdowns on 78 receptions, while being targeted 114 times.
• Over the course of 15 games played last season, George Kittle had 60 catches (4.0 receptions per game on 5.7 targets per game) for 765 yards and 11 receiving touchdowns (third in the NFL).
• Deebo Samuel had 56 catches for 632 yards and two receiving touchdowns. He averaged 4.3 yards per game over 13 games and was targeted 94 times.

Defense

• In 2022, Nick Bosa amassed 18.5 sacks to go with 19.0 TFL and 51 tackles in 16 games. He ranked first in the NFL in sacks.
• Fred Warner had 130 tackles, 3.0 TFL, two sacks, and one interception.
• Dre Greenlaw intercepted one pass on top of127 tackles, 3.0 TFL, and six passes defended in the 2022 season.
• Talanoa Hufanga totaled 2.0 sacks as well as 5.0 TFL, 95 tackles, and four interceptions.

Pittsburgh Betting Info

• Pittsburgh went 10-6-1 ATS last season.
• Against the spread, as underdogs of 2.5 points or more, the Steelers went 5-4-1 last year.
• A total of seven of Pittsburgh games last year hit the over.
• The Steelers were underdogs in 11 games last season and won five (45.5%) of those contests.
• Pittsburgh was 4-6 last season when entering a game as the underdog by +110 or more on the moneyline.
• Bookmakers have implied with the moneyline set for this matchup that the Steelers have a 47.6% chance to win.

Steelers Stats (2022)

Pittsburgh's Key Players

Offense

• Last season in 17 games, Najee Harris racked up 1,034 yards rushing and scored seven rushing TDs. He averaged 60.8 yards per game and 3.8 per attempt (41st in NFL).
• Harris also was a piece of the pass attack with 229 receiving yards (13.5 per game) on 41 receptions (2.4 per game), targeted 53 times. He had three receiving TDs.
• In 13 games, Kenny Pickett had 2,404 passing yards, throwing for seven TDs with nine INTs and completing 63.0% of his passes.
• He added 237 yards rushing, while scoring three TDs on the ground (averaging 18.2 yards per game and 4.3 per carry).
• George Pickens put up 801 yards receiving and four TDs on 52 receptions while being targeted 84 times last season.
• Diontae Johnson was targeted 147 times, resulting in 86 receptions for 882 yards and zero receiving TDs.

Defense

• Alex Highsmith had 63 tackles, 12.0 TFL, 14.5 sacks, and one pass defended in 2022.
• Cameron Heyward had 10.5 sacks to go along with his 14.0 TFL and 74 tackles in 17 games.
• Elandon Roberts had 104 tackles, 10.0 TFL, and 4.5 sacks in 2022 for the Dolphins.
• Minkah Fitzpatrick put up 1.0 TFL, 96 tackles, and six interceptions over 15 games.