Murray played six weeks in a row, winning three tournaments, to book his spot at the eight-man event in London, but the odds are now firmly against him progressing from the group.
The Scot’s 6-4 6-4 defeat by debutant Nishikori means he will almost certainly need to beat the other two players in Group B, Roger Federer and Milos Raonic, to stand a chance of reaching the semi-finals.
Even that might not be enough, with a straight-sets loss leaving him vulnerable when the final round-robin calculations are made.
It was not hard to find the weak spot in the former Wimbledon champion’s game, Murray winning only 26 per cent of points on his second serve.
The 27-year-old had not dropped a set in three previous matches against Nishikori, who has had by far his best season on tour, capped by a run to the US Open final.
Murray said: “I don’t necessarily go into every match against all the top players expecting to win. You want to win the match, that’s obviously the goal all the time.
“But you’re competing against the best players in the world, and Kei is obviously playing well just now, so I knew that this was a possibility.
“But it’s still obviously disappointing to lose the first match and I would have liked to have done better.
“I didn’t serve well enough. I would say that was the biggest difference in the match.
“He was able to dictate a lot of points, especially behind my second serve.”
Murray took only two days off following his run of consecutive tournaments and called the trainer after the seventh game of the second set to have his left calf rubbed.
But he insisted there was no problem, saying: “I just felt a slight tightness in my calf, so I asked him to come and have a look. It was fine. I moved fine after that. Just a precaution.”
Nishikori is the first Asian singles player to qualify for the end-of-season tournament and he admitted he was tight at the start.
He said: “The stadium is huge. I tried not to look up too much because there were too many people up the top.”