Erik ten Hag suffered his first defeat as Manchester United manager when Atletico Madrid celebrated a 1-0 win in Oslo in last season’s friendly.
Joao Felix scored the only goal of the game three minutes from time after a lively encounter that saw Fred sent off in added time.
– Dawson: Ten Hag can take positives from the pre-season tour
Marcus Rashford and Harry Maguire both had chances for United, who suffered their first setback of the summer after three wins and a draw on their tour of Thailand and Australia.
Ten Hag hinted at his starting XI for next week’s Premier League opener against Brighton by picking a strong side against Atletico which included Maguire, Rashford, Bruno Fernandes and Anthony Martial.
Jadon Sancho would also have started after the Oslo trip but missed after falling ill overnight.
New signings Lisandro Martinez and Christian Eriksen made their debuts on the bench following their move to Old Trafford.
Eriksen impressed after coming on as a second-half substitute, but the Danish midfielder couldn’t find a way to break through a stubborn Atletico defense that held up despite intense pressure from Ten Hag’s side.
Rashford and Maguire both had good scoring chances but it was Joao Felix who capitalized on his chance late on, firing deep past De Gea.
Fred, booked in the first half, was then sent off for receiving a second yellow card after a tackle against Alvaro Morata.
Ten Hag have another chance to reign over their players ahead of the new season with a friendly against Rayo Vallecano at Old Trafford on Sunday.
He will give the squad players a chance to improve their fitness against the Spanish side, while Cristiano Ronaldo has also hinted he will play a role.
Ronaldo returned to Carrington last week after missing the tour due to a family issue.
The 37-year-old is keen to leave the club this summer, although United have so far been adamant he is unavailable for a transfer.
The Portuguese striker has one year left on his contract plus an option for another season and has been linked with moves to Atletico Madrid, Chelsea and Bayern Munich.