Nishikori, the fifth seed, cruised past the world No. 7 at Vienna's Stadthalle, winning 6-3, 6-1 to set up a semifinal with Kazakhstan's Mikhail Kukushkin on Saturday.
The Spaniard broke Anderson twice in the second but didn't get another chance on the South African's serve in the final set.
With a victory on Sunday, Anderson will qualify for the ATP Finals.
Nishikori leads the field with 60% of second-serve return points and 38% of return games won in the tournament before the match, and the semifinal confirmed the trend as Kukushkin won just 57% of second serve points.
The eighth-ranked Anderson defeated Kei Nishikori 6-3, 7-6 (3), handing his opponent his ninth straight defeat in a final.
Anderson joins Rafael Nadal, Novak Djokovic, Roger Federer, Juan Martin del Potro and Alexander Zverev in qualifying for the ATP Finals, with at least two spots up for grabs in the French capital next week.
Red Sox top Dodgers for 4th World Series title in 15 seasons
Not my start in Game 2 and coming out of the bullpen in Game 3 and all that, but this one right here - being World Series champs. Shortly after hoisting the World Series trophy above his head Sunday night, he had a new request for the Boston brass.
Anderson has a shot at a fifth career title and second of the year after winning in NY in February.
"You have to win a lot of big matches against the best opponents in the world to book your spot there, so it's fantastic to be amongst the best eight players in the world", Anderson said.
He beat Nishikori in February to win the New York Open.
NY and the 32-year-old's previous three career wins came in Johannesburg, Delray Beach and Winston-Salem were all at World Tour 250-level. "Any time you make a final, you want to put the history behind you and it was always going to be a tough match. I couldn't be more pleased to have kept at it and finally broken through at this level".
He will meet Nishikori for the eight time overall with the Japanese leading 4-2 in their tour-level meetings.
A victor of 11 ATP events, Nishikori hasn't triumphed since winning in Memphis in February 2016.