Oxford shrugged off losing manager Liam Manning hours before kick-off to hammer Chelsea Under-21s 5-0 and go through to the knockout stage of the EFL Trophy.
Craig Short oversaw the game as Oxford's interim head coach after Manning was unveiled at Bristol City.
Josh Murphy scored twice, with Sonny Perkins, Jordan Thorniley and Mark Harris also on target at the Kassam.
Leo Snowden, at 15 years and 157 days old, came off the bench to become the youngest player in Oxford's history.
"To be given the opportunity to be on the bench was amazing and to be able to get on for 10 minutes, even though I was huffing and puffing, was a great experience and I'm looking forward to having more opportunities in the future," Snowden told BBC Radio Oxford after the game
"The main aim is in four-five years time to be able do it on a regular basis, so it's great to break the record in the first place but I want to get more than one game in the next couple of years.