Denver Broncos vs San Francisco 49ers

San Francisco heads out on the road after struggling in Week 1 in their other road game, losing 19-10 at Chicago as a TD favorite. QB Trey Lance (ankle) is out with an injury so backup Jimmy Garoppolo will start. Star TE George Kittle has yet to play with a groin injury. The 49ers are 12-27 ATS on the road after allowing 9 points or fewer in the last game, plus 22-38 ATS away after a win by 14+ points. Denver's defense has been terrific, Top 10 in yards allowed and third in points surrendered (18.9 ppg). The 49ers prefer balance on offense but the Denver defense is third against the run. New QB Russell Wilson (2 TDs, 1 INT) leads a balanced Bronco offense that has thrown more than it has passed with the ground attack averaging 4.9 yards per carry. They've struggled in the red zone so far but that will change as there are so many talented pieces. Play Denver.

Jimmy Garoppolo is expected to see some action for the first time since his ACL injury last season, but Nick Mullens and C.J. Beathard will get most of the snaps following the 49ers' 17-9 win over Dallas in the first week of preseason. Beathard finished 13 of 17 for 141 yards and a touchdown while Mullens was 11 of 17 for 105 yards, evening Kyle Shanahan's preseason record at 4-4-1 ATS. Denver lost to Seattle in Vic Fangio's second game as head coach, and the Broncos' quarterback depth isn't nearly as experienced with Drew Lock, Kevin Hogan, and Brett Rypien. Lock finished 17 of 28 for 180 yards against the Seahawks while Hogan completed 3 of 7 for 27 yards. Joe Flacco played one series and was 3 of 4 for 19 yards, and he doesn't expect to see much action in this matchup. The Broncos are still adjusting to a new coach and offense while San Francisco wants to continue to build a winning attitude after last year's disappointment and Garoppolo's injury. Take the 49ers.

Denver has won three straight, but it's still less than a touchdown favorite against the 2-10 49ers. That is due to the possibility of it being a flat spot for the Broncos after a big home win over Pittsburgh and then winning on the road 24-10 at Cincinnati. Rookie Phillip Lindsay rushed for a career-high 157 yards and two touchdowns and Case Keenum completed 12-of-21 passes for 151 yards. San Francisco quarterback Nick Mullens finished 30-of-48 for 414 yards, but the Niners couldn't get their running game going, rushing for only 66 yards on 2.9 per carry. Still, Mullens performed well considering Seattle is one of the toughest places to play and now he gets another chance at home. The Broncos are 5-12-1 ATS their last 18 games after allowing 15 or fewer points in their previous game and San Francisco has covered the number five of its last seven December games. Surprisingly, these teams have similar offensive statistics with Denver averaging 365.7 total yards and 23.0 points compared to 363.2 and 21.2 for the 49ers. The points loom large in this matchup, so take the 49ers.

Denver scored twice in the final quarter to defeat the Bears 24-17 in Vance Joseph's first game as coach. QB Trevor Siemian cemented his standing as starting quarterback in completing six-of-seven passes for 51 yards while Kyle Sloter was five-of-six for 94 yards and a touchdown. The Broncos also gained 106 yards on the ground. There still is healthy competition at the quarterback position as the Broncos head to San Francisco and the Broncos also rushed for 106 yards on 26 carries, including De'Angelo Henderson's 41-yard score with 1:49 left in the game. The 49ers also had a win in their new head coach's first game 27-17 over Kansas City as Matt Barkley completed 10-of-17 for 168 yards and CJ Beathard was 7-of-11 for 101 yards. Projected starter Brian Hoyer completed one pass in limited action in Kyle Shanahan's coaching debut with the Niners. Denver has won six of its last seven preseason games at San Francisco and 20 of its last 28 on the road against NFC West teams in exhibition play. The Broncos still have a big edge in talent against the rebuilding Niners. Play the Broncos on the moneyline.

San Francisco coach Chip Kelly was not happy with his team's performance, especially the two fumbles, in the 49ers loss to Houston on Sunday. The good news is that the Niners rushed for 236 yards on 6.9 yards per carry. Blaine Gabbert was 4 of 10 for 63 yards and Jeff Driskel finished 4 of 12 for 20 yards and also rushed for 61 yards. Thad Lewis was 12 of 21 for 97 yards, but tore his ACL and is out for the year, so the 49ers signed Christian Ponder, who played with Minnesota from 2011-14. Colin Kaepernick didn't play due to a sore shoulder. Mike Davis was a bright spot in rushing for 72 yards on five carries. Denver shut out Chicago 22-0 as Mark Sanchez made a case for the starting job, completing 10 of 13 passes for 99 yards with one interception. Trevor Siemian contributed to the cause by going 7 of 12 for 88 yards. Rookie Paxton Lynch was 6 of 7 for 74 yards. It was hard to tell if Denver was that good or if Chicago was that bad as the Bears looked absolutely horrible on offense with 130 total net yards. The 49ers and Broncos will practice twice against each other before they play for real on Saturday, so there will be some familiarity. The Broncos also lost defensive end Vance Walker for the season with a knee injury. Laying more than a field goal in preseason can be dangerous and the line is inflated a point or two due to last week's results. Grab the points and play the 49ers.