Jimmy Garoppolo's addition last season immediately turned around the NFL fortunes of the San Francisco 49ers.
Now they will have to go back to life before Garoppolo for the rest of the season.
The Niners announced Monday that Garoppolo tore the anterior cruciate ligament (ACL) in his left knee while making a cut late in the loss at Kansas City, ruling him for the rest of the season.
"It is very unfortunate," coach Kyle Shanahan said.
"I'm not going to sugarcoat it. It was hard waking up today.
"We were down and disappointed about it because we were looking forward a lot to playing with Jimmy this year and going through the good and the bad knowing that he'd benefit from all of it.
"Now we don't get to do it.
"I know Jimmy is really down about it and so are we but it's still going to be all right."
The injury deals a serious blow to the 49ers (1-2), who had planned their rebuild around Garoppolo and now must turn again to C.J. Beathard at quarterback.
Garoppolo will undergo surgery and should be ready to play again next season.
The Niners struggled with Beathard and Brian Hoyer last season before the mid-season addition of Garoppolo from the New England Patriots changed their fortunes.
San Francisco won the final five games last year after Garoppolo took over as starter and the team rewarded him with a $137.5 million ($A189 million), five-year contract.
