Some Arsenal fans booed when Oxlade-Chamberlain, who helped create Robin van Persie's equaliser, was taken off.
"I've been a manager for 30 years and have made 50,000 substitutions. I don't have to justify every one," he said.
Arsenal trail fourth-placed Chelsea by five points in the Premier League race for Champions League qualification.
Oxlade-Chamberlain was one of the brighter elements of Arsenal's performance at the Emirates.
The 18-year-old, making his first Premier League start, set up Van Persie during a period when Arsenal had begun to dominate.
"I can understand that the fans are upset about the substitution, especially when it doesn't work, but he had started to fatigue," Wenger said of his decision to substitute the former Southampton winger.
"He was sick in the week. Arshavin is captain of the Russia national team. You have an 18-year-old kid making his first Premier League start and a player who's captain of his country and they are querying the substitution?"
Asked how the defeat affected his team, Wenger said it was a match Arsenal "couldn't afford to lose" before adding: "It leaves us in a very difficult position."
United manager Sir Alex Ferguson felt his side deserved the victory which keeps them three points behind leaders Manchester City.
"I felt eventually we were the better side," he said. "Credit to the players at the back, who did a great job.
"We rode our luck a bit but on the counter-attack I thought we could have scored more goals."
Asked about the pursuit of City, he said: "It's going to be hard for both of us to collapse."
The result left Spurs five points behind United and eight adrift of City, with 16 matches remaining.
Ferguson added: "It was a really disappointing result for Spurs - they deserved better but football's a funny game.
"Come March and April you never know what's going to happen. At the moment we've got a few points clear, the both of us."
United's win came at a cost as Phil Jones was carried off on a stretcher after 15 minutes with ankle ligament damage.
In addition, Nani left the Emirates in a protective boot after going off injured in the second half, Wayne Rooney was hobbling at the final whistle and Michael Carrick suffered a sore hamstring.
MAN UTD's NEXT FIVE LEAGUE GAMES
The injury to Jones is particularly worrying for United as they were without Rio Ferdinand, who missed the game with a suspected back injury, and Nemanja Vidic, who is out for the rest of the season following knee surgery.
Ferguson is also without Anderson, Tom Cleverley, Ashley Young, Michael Owen and Darren Fletcher.
"It's not good news for us," Ferguson said. "I think Jones will be out for a few weeks - it's ankle ligaments.
"Carrick was feeling his hamstring in the second half and he just had to sit in the middle of the pitch."
A key figure in United's victory was winger Antonio Valencia, who headed the first goal and created the winner with a mazy run.
"He was absolutely fantastic; he was really in top form," Ferguson said of the former Wigan man.
"In the last few weeks he's really come into his game. He's got over the bad injury he had last season and he's getting better all the time."
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