Mikel Arteta's team travelled for Sunday's London derby without the services of Martin Odegaard due to injury, which opened up a spot for Nwaneri to make the matchday squad.
The teenager was named on the bench as Fabio Vieira started in the number 10 position, during which the Portuguese scored a stunning long-range goal to put the Gunners 3-0 up.
With a dominant Arsenal side out of sight in the dying embers, Arteta brought on Nwaneri in added time, as the Englishman became the Premier League's youngest-ever player at 15 years and 181 days.
Nwaneri broke the previous record set by Harvey Elliott, who was 16 years and 30 days when he made his top-flight debut for Fulham, and Xhaka - who is doing his coaching badges with the Arsenal youth teams - has not been able to stop singing the midfielder's praises.
"We have to check the passport first! I am joking. To have a guy who is 15 and is nearly 15 years younger than me," Xhaka told reporters after the game.
"He looks old when I see him, but the club can be proud of a player like him. He has a big future. I am doing my coaching licence and I have trained the under-16s.
"You can see a big difference with him and the other guys. He is very, very special. You have to protect him as he is very young but if he keeps going like this with his hard work he has a big, big future.
"It's not only me that feels old. I spoke with one Brentford guy and I told him this guy was 15 and he looked at me and said: 'F*** me, we are looking old! When you have 15 years difference you think 'OK, the time is not gone but it is on the way'. But we are enjoying him, he is enjoying us as he has the quality."
After handing Nwaneri his Premier League debut at the Brentford Community Stadium, manager Arteta explained that he had a "gut feeling" about the youngster, who has quickly risen through the ranks at youth level.
"It was a pure gut feeling. I met the boy (and) really liked what I saw. Per Mertesacker and the academy staff are giving me really good information, Edu as well," Arteta said at his post-game press conference.
"I met him, he's trained a couple of times with us. Yesterday he had to come because we have injuries, especially the injury of Martin (Odegaard), and then I had that feeling from yesterday that if the opportunity could come that I was going to do it and I just done it.
"I told him yesterday that he was going to be with us and that I want him to experience how it is to be in the hotel, to do a preparation of the game to be around the boys and that he had to be ready.
"If you're going to be on that bench you have to be ready. The boy just looks in your eyes and he's ready. I don't know what it is for him. When I met him, when I look at him, I had that feeling."
Nwaneri - an England Under-17 international - has registered one goal and two assists in three Under-18 Premier League appearances this term and made his debut for the Under-21s against Blackburn Rovers on September 3, claiming another assist in that 4-1 win.
Goals from Vieira, William Saliba and Gabriel Jesus saw Arsenal claim a comfortable win over Brentford on Sunday lunchtime, and the Gunners head into the international break top of the table with 18 points from their opening seven matches.