Friday the 6 feet 9 inches tall Isner takes on the unseeded Yen-Hsun Lu of Taipei, while Fish is to meet the 8th seeded Somdev Devvarman of India.
In other action Thursday at Atlanta, the unseeded American Ryan Harrison upset the 4th seeded Xavier Malisse of Belgium 6-7(3-7), 6-4, 6-4; while the American qualifier Rajeev Ram upset the former number one Lleyton Hewitt of Australia 7-5, 2-6, 6-2.
The Atlanta Tennis Championships are part of the Olympus US Open Series which is composed of ten tournaments during the course of six weeks before the US Open begins August 29th.
The 29 year old Fish posted his best ever US Open result in a 2008 quarterfinal finish. In 2004, Fish won a silver medal in singles at the Olympic Games.
Isner, 26, in 2009 reached the fourth round at the US Open in his best career New York result.
Fish could meet Isner in an all-American Atlanta singles championship final Sunday.