Isner beat former world number one Lleyton Hewitt of Australia 6-4 4-6 7-6(5) while Anderson was too good for American Ryan Harrison 6-3 7-6(3).
The top-seeded Isner fired 21 aces on the way to beating Hewitt in a cracking match, giving him a chance at shedding his Atlanta bridesmaid's tag having been runner up twice previously.
The big serving American is seeking a seventh career ATP crown in the $US546,930 hardcourt event.
Hewitt looked set to complete an upset when holding triple break point in the seventh game of the third set but Isner fought back before winning it 7-5 in a tiebreak.
The six-foot-10 (2.08m) American moved to 24-6 in tiebreaks this year, the best on the ATP Tour.
Anderson needed just 91 minutes to beat the unseeded 21-year-old Harrison, riding a 91-percent conversion rate on first service points won and saving all five break point opportunities Harrison earned.
Harrison had two set points on his serve in the second set but could not close out, allowing Anderson to take the tiebreak 7-3.
The six-foot-eight (2.03m) Anderson will be chasing his third career ATP crown in his sixth final appearance having won in Johannesburg in 2011 and at Delray Beach in 2012.
He has been runner up twice already this year in Sydney and Casablanca.