Wawrinka, who won the Chennai tournament in India in the first week of the season for the three previous years, had treatment on his lower left leg at the end of the first set tiebreaker and twice again in the second set.
Third-seeded Nishikori took full advantage, converting his first break point in the second set to take a 3-1 lead when Wawrinka missed consecutive backhands. The No. 2-seeded Wawrinka broke back immediately, but dropped his serve again in the next game.
Wawrinka beat Nishikori in the semifinals of the U.S. Open last year; his only win in their last four matches. With his win Saturday, Nishikori has leveled up his career head-to-head record against the three-time major winner at 4-4.
Nishikori was making his seventh trip to Brisbane, and playing a semifinal for the fourth time. The Japanese star is still chasing his first Grand Slam title, with his best run at a major remaining his appearance in the 2014 U.S. Open final.
Defending champion and No.1-seeded Milos Raonic was to play seventh-seeded Grigor Dimitrov for the other spot in the final. Raonic, who beat Rafael Nadal in the quarterfinals, finished 2016 ranked at No. 3 but hasn’t added another title since winning in Brisbane for the first time.
U.S. Open finalist Karolina Pliskova was playing unseeded Alize Cornet in the women’s final on Saturday night.