With the 49ers needing to punch the ball in for a score, McCaffrey took the handoff and leaped over the offensive and defensive linemen to break the plane of the end zone.
McCaffrey looked to have plenty of momentum early, but that changed when he exited during the 49ers' next offensive drive and received sideline treatment.
The 49ers announced that McCaffrey was dealing with a thigh injury, forcing the team to finish the first half without one of its most versatile offensive weapons.
"It just sucks to me because that was one of those ones where I just felt like I could have got going," McCaffrey said during a post-game interview. "... I was just trying to keep it warm and not make it worse, but there's only so much you can do to get back to where you want to be. I'll be fine. I know that. I'll be all right."
After the game, quarterback Brock Purdy discussed the impact of losing McCaffrey and the offensive adjustments the 49ers had to make.
"Obviously, what he brings to the table in our offense and stuff, being able to run the ball with him, being able to throw the ball out of the backfield with him, line him up, throw him the ball, those are all things that we obviously love to do and stuff," Purdy said. "And when he's not there, then we got other guys that are open.
"And so, obviously, when he's not out there, it's new guys, young guys that have to come along and stuff, and I think they're doing a great job with that. [RB] Kaelon [Black] and [RB] Jordan James run the ball really hard and stuff."
McCaffrey offers a unique dimension to the 49ers' offense. As Purdy noted, the veteran running back is as dangerous as a receiver as he is as a runner.
"Obviously, what Christian can do out of the backfield as a receiver, receiving running back, that's the component too that, obviously, we want out there," Purdy said. "I'm not saying those other guys can't. It's just, Christian, he's a Hall of Famer with that.
"So, yeah, it obviously changes up our game plan and stuff, but we also have to be able to adapt and use our other guys in the ways that they're able to go and make plays."
McCaffrey returned in the third quarter but acknowledged that he wasn't at full strength.
"That's the whole point of not being able to play it at 100 percent," McCaffrey said. "When something like that happens, it sucks, but you've got to find a way to make it work, maybe at a slower speed. But I know I'll be all right. I know I'll get this thing back and be ready to go."
Fortunately, McCaffrey will have time to recover during the 49ers' bye week. San Francisco won't play again until November 8, when it hosts the Las Vegas Raiders at Levi's Stadium.
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