Minutes after the 38-27 defeat, Niners coach Kyle Shanahan said the fear is that Garoppolo suffered an ACL injury, which would almost certainly end his season.
Shanahan said the Niners would know for sure on Monday after Garoppolo undergoes further tests.
"Anytime you lose your starting quarterback, that is a big deal," Shanahan said. "It was when we lost our starting running back [Jerick McKinnon] too. So obviously, I feel for him personally. I know how disappointed he is. I haven't got a chance to see him yet. I feel for him."
Garoppolo's injury occurred with about 5:35 left in Sunday's game. On third-and-goal from Kansas City's 20, Garoppolo felt pressure from Chiefs defensive end Justin Houston on his right side. Garoppolo evaded Houston and scrambled down the left sideline.
After gaining 13 yards, Garoppolo had the choice between stepping out of bounds or staying in and taking a hit from a defender. He took an awkward step near the sideline with his left leg before ramming into Chiefs cornerback Steven Nelson at Kansas City's 7.
"That was, I think, that was his fault," Houston said. "I pray he's not hurt and it's nothing serious, but as a quarterback, you should step out of bounds. It's only an inch. An inch [gained] wouldn't have made a difference. You got the yardage you need, you step out of bounds. You've got to be smart, think about your team."
Garoppolo crumpled to the ground, where he received immediate medical attention. Eventually, Garoppolo was able to hobble to the sideline, where he sat on the bench and pointed to his left knee as the Niners medical staff surrounded him. He then entered the blue medical tent with C.J. Beathard replacing him.
Soon after, Garoppolo left the game on a cart and did not return.
"Jimmy was just trying to make a play," left tackle Joe Staley said. "We were trying to make a comeback."
Before the injury, Garoppolo was 20-of-30 for 251 yards with two touchdowns and no interceptions for a passer rating of 114.7.
Shanahan and some of Garoppolo's teammates said after the game that they initially thought Garoppolo had suffered a concussion. Others thought it might have been a shoulder injury, but replays showed that Garoppolo's left leg seemed to catch a bit on the grass as he turned upfield.
A disappointed 49ers locker room expressed regret about Garoppolo's injury but also did its best to make sure to support Beathard.
"It sucks," tight end George Kittle said. "Jimmy is a great quarterback, the leader of our team. But it's football, and it's next man in. That's just the nature of the game. Luckily, we have a guy who has been in the system and he's had success in C.J. So we're just going to look ahead and try to keep moving forward."
"It's a tough injury. I feel bad for Jimmy ... it sucks," Brady told WEEI on Monday. "You hate to see someone go down, someone I really like and have been friends with since the day he got here."
Brady suffered his own ACL tear in Week 1 of the 2008 season while also playing against the Chiefs.
According to Shanahan, the plan is to move forward with Beathard as the starter. On the play after Garoppolo's injury, Beathard hit Kittle for a would-be touchdown, though it was erased by an offensive pass interference call against the Niners.
Beathard did not attempt a pass that counted in Sunday's game, though he did start five games as a rookie last season, including San Francisco's first win of the season against the New York Giants. In seven games prior to Sunday's loss, Beathard completed 54.9 percent of his passes for 1,430 yards with four touchdowns and six interceptions for a passer rating of 69.2.
"I have got a lot of confidence in C.J.," Shanahan said. "He came in today, made a helluva throw on that fourth down. No hesitation. C.J. is a gamer. Everyone in here has a ton of respect for C.J., how he handles himself. He's a man out there, and he's a very good quarterback, and we're fortunate to have him."
Shanahan indicated that the Niners will need to add another quarterback to the roster or practice squad so that they will have three in the building. Any outside addition would be as a backup to Beathard.
As Garoppolo was receiving attention in the team's training room, Beathard stopped in to chat and tell Garoppolo he'd be praying for him.
"He told me to lead these guys," Beathard said.
As Garoppolo prepared to leave Arrowhead Stadium, his family awaited his departure just outside the Niners locker room as team owner Jed York and general manager John Lynch stopped to offer words of encouragement. Garoppolo soon emerged and spent a few quiet moments with his family. Then Garoppolo grabbed his crutches and got back on the golf cart to go to the team buses. On the ride up the ramp, Kansas City quarterback Patrick Mahomes and other Chiefs and Niners stopped him to offer their own words of support.
"Jimmy is our leader," fullback Kyle Juszczyk said. "He's a guy that we've been basing our offense around since he got here last year. So there's definitely going to be some adjustments, but I think we have got some of the best coaches in the business that make those adjustments, so I think they'll do their job and take care of things."
According to the Westgate Las Vegas SuperBook, the Niners went from 60-1 odds to 200-1 to win the Super Bowl and from 30-1 to 100-1 to win the NFC after Garoppolo's injury.
Garoppolo wasn't the only Niners star to leave Sunday's game with an injury. Cornerback Richard Sherman suffered a heel/calf injury late in the second quarter, an injury that not only kept him out for the rest of the game but also required a Niners staff member to assist him on his walk to the locker room at halftime.
Before departing, Sherman had two tackles and broke up a deep pass that Mahomes slightly underthrew for receiver Tyreek Hill.
Sherman was playing his third regular-season game after recovering from the torn right Achilles he suffered last November. He also had surgery to remove bone spurs from his left ankle in the offseason and missed practice Thursday with what the Niners called a heel injury.
Like Garoppolo, Sherman is expected to have further tests Monday. He departed the locker room with his left foot in a walking boot, and Shanahan said the injury was the same thing that bothered him during practice last week.