The 6-foot-10 Isner beat Lleyton Hewitt 6-4, 4-6, 7-6 (5) on Saturday, and the 6-8 Anderson topped American Ryan Harrison 6-3, 7-6 (3) in the night semifinal.
Isner is 5-3 as a pro against Anderson, and they played several times before that.
“We’ve been playing each other since, I think the first time was the fall of 2005 (when Isner was at Georgia and Anderson at Illinois),” Anderson said. “We both serve quite well. ... I definitely think there have been times when the success he’s had has pushed me to do well.”
Isner lost in the Atlanta finals in 2010 and 2011 to fellow American Mardy Fish.
“It’s my third final here, and I would certainly like to win it but I’m not putting any extra pressure on myself,” Isner said.
Isner took the first set against Hewitt, winning 88 percent of all points on first serve and 68 percent on second. The American had 21 aces after ringing up 50 in his first two matches of the tournament.
“My weapon is my serve,” Isner said after breaking the Australian with a cross-court forehand to end the set. “His weapon is his return so it was a fun match.”
Hewitt, the former world No. 1, began figuring out the booming serves and spinners, and broke Isner twice to win the second set.
“He anticipates so well,” Isner said after moving to 2-4 against Hewitt. “He’s not one of those guys that goes back to the fence and (waits for hard serves). It’s similar to (No. 1 Novak) Djokavic. He just absorbs 140 mph serves from me. If I don’t hit my spot, it’s coming back.”
Hewitt was not available after the match because he and countryman Chris Guccione were resting for a late doubles semifinal match against Britons Colin Fleming and Jonathan Marray.
In the third set, the players stayed on serve until the tiebreaker, but not without scares. At 3-3, Isner fought off triple service break with five straight service winners.
“It doesn’t look good for me if I go down a break 4-3 in the third,” Isner said. “That was a huge game, massive game, and . . . saved the match for me.”
He also survived a break before going up 6-5.
Isner took leads of 3-0 and 4-1 in the tiebreaker. Hewitt clawed back to 5-5 with one more serve.
After returning it, Isner moved forward. That had not worked well earlier as he’d bumped several short Hewitt volleys back into the net. But the big guy didn’t want to bang balls back and forth.
A defensive backhand slice went hard left beyond Hewitt’s to put Isner up 6-5.
“A guy like (Hewitt), chances are he’s not going to tighten up and make a loose mistake. And he’s better than me from the baseline,” Isner said. “At that moment, I was a little bit tired . . . and I wanted to play that point aggressively.”
When Hewitt sent Isner’s next serve far wide right, the American pushed his ATP-best tiebreaker mark to 24-6 while Hewitt fell to 5-6.
In the only Isner-Anderson match this year, Isner won in straight sets in February in Delray Beach, Fla.
The second-seeded Anderson, from South Africa, is ranked No. 21 in the world, and will move into the top 20 with a win.
Isner is No. 22 with a chance to pass Sam Querrey (20) as the highest-ranked American with a win.