San Francisco enacted Plan B when Trey Lance broke his ankle against Seattle, so Jimmy Garoppolo will lead the 49ers against the Denver Broncos on Sunday.
Denver was a potential landing spot for Garoppolo when it became known that the Niners were moving towards making Lance their starter for 2022, but they pulled off a huge trade for Russell Wilson instead.
The former Seahawks star was given a rude welcome back to Seattle in Week 1 and there were still signs of rustiness in his game during last Sunday's mistake-ridden win over the Houston Texans.
Penalties have been killing Denver's drives, while injuries are already beginning to bite hard, so rookie head coach Nathaniel Hackett will have his work cut out to get the better of Kyle Shanahan and the best back-up QB in the business in Sunday's prime-time match-up.
San Francisco 49ers @ Denver Broncos
Empower Field at Mile High, Denver
20:20 ET, Sunday September 25th
|How to watch|
NBC, live streaming on NBCSports.com, the NBC Sports app, Peacock and fuboTV
|Odds||SF 49ers -125, DEN Broncos +105|
It was awful to see Lance carted off the field in the first quarter of last week's 27-7 win over the Seahawks after absorbing a big hit on a designed quarterback keeper.
His misfortune gives Garoppolo, who underwent surgery on his throwing shoulder this past offseason, a chance to add one final chapter to his San Francisco story.
Jimmy G would be leading another team right now were it not for the surgery and a high price tag, but the Niners get to cash their insurance policy in early and go with a veteran arm again.
Garoppolo is 37-16 as a starter in the NFL and has taken his team to two NFC Championship Games and a Super Bowl - in stark contrast to the inexperienced Lance, who has tremendous upside but was always going to be prone to rookie-type errors in 2022.
The 30-year-old showed no signs of rust in dicing the Seahawks' defense for 154 yards, a TD and no picks last week and should be even more comfortable in re-assuming leadership of the team at Mile High.
Wide receiver Brandon Aiyuk led the 49ers in targets, receptions, and yardage. The 24-year-old should see plenty of action again with San Francisco expected to return to the air against the Broncos.
Deebo Samuel, however, could see more snaps as backfield runner - a role he shone in last season. The hybrid receiver/rusher had five receptions for 44 yards and four carries for 53 yards last Sunday.
Tight end George Kittle is expected to be back to bolster the visitors' offense after missing the first two weeks with a groin injury.
The Broncos' top cornerback, Patrick Surtain, is a doubt to face the Niners after sustaining a shoulder injury last weekend.
Denver's top wideout, Jerry Jeudy, also looks likely to miss out this Sunday after exiting the Broncos' Week 2 win over the Texans in the first half with a rib/shoulder issue.
It was noticeable how Wilson, who threw for 219 yards with one touchdown and one interception, struggled more once Jeudy was in the locker room.
Courtland Sutton became his favorite target - grabbing seven receptions for 122 yards as Wilson looked his way 11 times against Houston.
Denver could dial up more short passes to their brilliant backfield duo of Javonte Williams and Melvin Gordon and look to set up screens to get the chains moving.
The Broncos struggled on third downs against the Texans, converting only three of nine, and it won't get any easier for them against a San Francisco unit that held the Seahawks to just 49 yards on the ground.
The longest run they allowed was just eight yards, which forced their opponents to become one-dimensional on offense.
Nick Bosa continued his fine start to 2022 by recording two sacks and two QB pressures against Seattle, which augurs well for a game of cat-and-mouse with Wilson, who was sacked three times last week.
San Francisco's ability to dominate on defense could ensure the hosts win the early field position battle and set Garoppolo up with enough chances to get the Niners on the board.
DeMeco Ryans' unit is ranked first in the NFL through two weeks, second against the rush and top-ranked against the pass.
Just comparing these two teams' respective results against Seattle should give enough clues about which one is in better shape with San Francisco, -110 to cover a -1.5 Spread, ready to be galvanized by Garoppolo's return to starting duty in Denver.