Isner advanced with a 6-4, 4-6, 7-6 (7-5) decision over Australian Lleyton Hewitt. The 6-foot-9 American, who has twice finished as runner-up in Atlanta, reeled off 21 aces in the victory.
Isner fell to fellow American Mardy Fish in both the 2010 and 2011 finals and is looking for his seventh career ATP Tour championship.
This time he will face South Africa's Anderson, who dispatched American Ryan Harrison in Saturday's second semifinal 6-3, 7-6 (7-3).
Anderson is seeking his first title of 2013 and third overall.