He's the first South African to reach the Finals series since Wayne Ferreira in 1995.
Nishikori was unable to find a way back in the first set and was consigned to defeat after Anderson's serve and forehand proved to be potent in a second-set tie-break, a 13th ace sealing the title.
"It's fantastic. It's been a huge goal of mine all year", Anderson said after lifting the trophy.
Nishikori has a 4-2 record against Anderson from six previous meetings, including a 6-1, 3-6, 7-6 (4) win in NY in February.
"You've been a world-class player year in and year out so best of luck for the rest of the year", he said. His fifth career title marks his first outside the ATP 250 level.
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Man City boss Pep Guardiola says the progress made by Mauricio Pochettino and his Tottenham side have proved him wrong. "Because we play one of the best teams in Europe and the world".
"And just London, the event itself, I've heard so much about it - a great arena, a great atmosphere - and to do it by winning my first 500 here in Vienna, as well, is a great combination". Each of the World No. 8's previous trophy wins - in Johannesburg, Delray Beach, Winston-Salem and NY - came at ATP World Tour 250-level events.
"The score might look easy, but the match was very tough", he said.
8, one hour and 55 minutes to get past Nishikori, earning his fifth career title and his second this season after taking the New York Open title in February, reports Efe.
He will meet Nishikori for the eight time overall with the Japanese leading 4-2 in their tour-level meetings.
After closing out the first set, Anderson brought the second set to a tiebreak where his big serving made the difference.