Now in ninth place, Nishikori with a win could move to within 125 points of the cut for the eight-man event in London next month.
The identity of the last two ticket holders will be determined at the Paris Masters starting on Monday, with Nishikori still in with a shout of making the elite eight-player cast list.
After the win, Anderson improved his head-to-head record against Nishikori to 4-3, earning his second victory in a row this year against the Japanese player, following his NY semifinal triumph.
"It's fantastic. It's been a huge goal of mine all year", said Anderson.
Kevin Anderson with his winning trophy at the ATP Erste Bank Open 500 in Vienna.
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A tight second set went to a tiebreak with Anderson landing his 13th ace of the match to win his landmark title.
On Saturday, he missed three break points in the first set before finally breaking in the 10th game with an aggressive forehand victor.
Earlier in the day, Nishikori defeated qualifier Mikhail Kukushkin from Kazakhstan 6-4, 6-3.
Anderson will be the first South African in 23 years to feature in the season-ending tournament in London next month after a 6-3 7-6 (7-3) defeat of Nishikori.
Anderson broke in the fourth game of the match to lead 3-1 when a powerful backhand forced an error from the fifth seed.
The towering 32-year-old is also guaranteed to finish the year in the top 10 for the first time, reward for claiming the fifth singles title of his career. Copil has two after also beating No. 6 Marin Cilic in the second round.