Zverev, at 21, will be the youngest semi-finalist at the eight man end of season championships since Juan Martin del Potro in 2009.
"It's obviously great getting to the semi-finals," said Zverev. "But the tournament isn't over. I am in the semi-finals. There's only good opponents left. There's only the best in the world.
"I'm playing Roger and it is going to be a very difficult but we'll see how far I can go."
Zverev’s victory nullified the stakes in the Friday night match between top seed Novak Djokovic and the fifth seed Marin Cilic.
Djokovic, who is seeking a record equalling sixth title, will advance as group winner following his successes over Zverev and Isner and will play the fourth seed Kevin Anderson in the last four.
The omens are bleak for Anderson. Djokovic beat him in straight sets in the Wimbledon final in July.