The three-time Grand Slam winner, who is hoping to keep hold of the number one world ranking before the end-of-season tournament is over, battled to a 6-7(9) 6-4 6-4 victory in three hours and 20 minutes.
It took 87 minutes for the first set to be won, with neither player able to snatch serve, although Nishikori had more opportunities as he created three break points, but failed to convert them.
A tie-break was needed to separate the two, and after Murray took a 5-6 lead, Nishikori fought back with a single break point to seal it 11-9.
Momentum was snatched back by Murray in the second set as he went a break up at the first time of asking, and he managed to hold off a late surge from his opponent to force a deciding set.
The Wimbledon champion took control of the court by moving into a 5-1 lead, but Nishikori delayed his competitor's victory by breaking back.
It was not enough to put Murray off his stride, though, as he held his next service game to claim an important victory at the O2 in London.