Manchester United goalkeeper Ben Foster was left rueing his luck as the club's 23-match unbeaten home run in the Champions League came to an unexpected end.
A goal by Rodrigo Tello after 20 minutes gave Besiktas their first win at the fifth attempt in Group B.
Foster was left stranded as Tello's effort rebounded off left-back Rafael and deceived him.
It was a cruel blow for Foster on his return between the posts for United for the first time in a month.
He last started for the club against Barnsley in the Carling Cup but went on to play two games for England, including the defeat by Brazil.
Foster then expressed his frustration at dropping down the pecking order at United with the World Cup on the horizon.
However manager Sir Alex Ferguson felt no blame should be attached to Foster for the decisive strike.
He said: "The goal followed a deflection off Rafael and we were chasing the game. Deflections off the body have a certain speed and that can cause a problem."
With qualification to the last 16 already assured, Ferguson handed starts to the likes of Federico Macheda, Danny Welbeck, Gabriel Obertan and Darron Gibson.
United were looking for the point that would have seen them finish as group leaders, only for his inexperienced side to come up short.
They almost drew level, however, in stoppage time but Besiktas goalkeeper Rustu made two superb saves in quick succession from Macheda and then Wes Brown.
Ferguson said: "I thought we needed a bit of composure. The young players were a bit anxious and that is understandable in a way.
"It was an experimental line-up in a way. We have to be fair in the way we assess the players in these games.
"The value is the trust we have got in playing these young players. They are potentially top players.
"The important thing is, though, they showed a good level. In the first half we had good opportunities but got caught on the counter attack."
United had a claim for a penalty dismissed late on by referee Stephane Lannoy when substitute Patrice Evra appeared to be blocked by Ibrahim Kas.
Evra appealed in vain and Ferguson questioned the decision after feeling they also had a valid spot-kick rejected in the draw against CSKA Moscow last time around.
"I was right to be agitated, " said the United boss. "If you can't give one like this and the one against CSKA Moscow then you are in trouble.
"It's a penalty kick - that's two games in a row they have denied us stonewall penalties but what can you do about it?"
Besiktas coach Mustafa Denizli said: "The whole world knows how big a team United is at Old Trafford, so we are very pleased with this result. It is a great night for Turkish football."Reuse content