The Real Madrid forward scored France's only goal in the 1-0 win, but immediately felt discomfort in his knee during the shot and was unable to celebrate properly.
Mbappe received treatment on the pitch before briefly attempting to continue. He then went down again and requested to be substituted, leaving the field limping in the 58th minute.
France subsequently confirmed that the 27-year-old would leave the national team camp and return to Madrid for further treatment.
“Kylian Mbappe injured his knee while scoring the winning goal and has suffered a tendon injury; he will return to Madrid for treatment,” the French Football Federation said.
The extent of the injury will be assessed in Madrid, with the first medical tests scheduled for Saturday.
Zinedine Zidane, taking charge of France for the first time, admitted the situation was concerning and said there was no reason to risk aggravating the problem.
“Unfortunately, Mbappe’s injury is not going well. I think he is going to have to return to Madrid. We are not going to take any risks,” Zidane told TF1.
“He suffered hyperextension in his knee when he shot. It is not exactly a good indication that he can continue playing.”
The injury is particularly concerning for Real Madrid because Mbappe had previous problems with the same knee last season.
He is the second Real Madrid player to return from the France camp with a knee injury in recent days, following Ibrahima Konate, who suffered a minor sprain.
Mbappe's injury also brings an early setback to Zidane's first international camp, with France still having three matches remaining during the current international break.
The forward's goal was his 67th for France, but his night ended moments later when the injury forced him from the pitch.
Real Madrid will now await the results of Saturday's examinations before determining how long their leading forward could be sidelined.