Murray and Skupski survived a nail-biter in the first round but were unable to produce another comeback, going down 6-3 6-4 at Ariake Tennis Park.
It has been a difficult season for Murray and his lack of confidence was clear at times, while Skupski also missed some key shots, and one break in each set was enough for the impressive Japanese duo to progress to the quarter-finals.
Murray said: “We’re disappointed to lose, obviously. The Olympic Games comes round once every four years and everyone wants to do well, everyone dreams of coming in and winning a medal.
“It was a tough match for us today. I think the other guys played very well, especially at the start to put us under the pump a bit. Just a tough day.”
This was Murray’s fourth appearance at the Olympics and he had to digest another early loss after only one win in three Games alongside his brother Andy.
It is not unusual for doubles players to compete into their 40s and, asked if he could have another shot in Paris in 2024, Murray said: “Maybe.
“I’ll be 38 then. There’s plenty of guys here still going strong at that age so we’ll see. If I am there, I guess it’s testament to the longevity of my career to play at that level for however many years.”
Andy Murray and Joe Salisbury will play their second-round match against German duo Kevin Krawietz and Tim Puetz on Tuesday, while Liam Broady takes on Hubert Hurkacz in the second round of the singles.
Andy Murray pulled out of the singles on Sunday due to a thigh strain.